Principles of Immunotherapy: Implications for Treatment Strategies in Cancer and Infectious Diseases

The advances in cancer biology and pathogenesis during the past two decades, have resulted in immunotherapeutic strategies that have revolutionized the treatment of malignancies, from relatively non-selective toxic agents to specific, mechanism-based therapies. Despite extensive global efforts, infectious diseases remain a leading cause of morbidity and mortality worldwide, necessitating novel, innovative therapeutics that address the current challenges of increasing antimicrobial resistance. Similar to cancer pathogenesis, infectious pathogens successfully fashion a hospitable environment within the host and modulate host metabolic functions to support their nutritional requirements, while suppressing host defenses by altering regulatory mechanisms. These parallels, and the advances made in targeted therapy in cancer, may inform the rational development of therapeutic interventions for infectious diseases. Although “immunotherapy” is habitually associated with the treatment of cancer, this review accentuates the evolving role of key targeted immune interventions that are approved, as well as those in development, for various cancers and infectious diseases. The general features of adoptive therapies, those that enhance T cell effector function, and ligand-based therapies, that neutralize or eliminate diseased cells, are discussed in the context of specific diseases that, to date, lack appropriate remedial treatment; cancer, HIV, TB, and drug-resistant bacterial and fungal infections. The remarkable diversity and versatility that distinguishes immunotherapy is emphasized, consequently establishing this approach within the armory of curative therapeutics, applicable across the disease spectrum.

[1]  R. Lerner,et al.  Evidence for the production of trioxygen species during antibody-catalyzed chemical modification of antigens , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M. Baer,et al.  An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity , 2008, Infection and Immunity.

[3]  G. Pantaleo,et al.  Targeted Immune Interventions for an HIV-1 Cure. , 2017, Trends in molecular medicine.

[4]  G. Freeman,et al.  Combination cancer immunotherapy and new immunomodulatory targets , 2015, Nature Reviews Drug Discovery.

[5]  M. Hallek,et al.  A Novel Recombinant Anti-CD22 Immunokinase Delivers Proapoptotic Activity of Death-Associated Protein Kinase (DAPK) and Mediates Cytotoxicity in Neoplastic B Cells , 2016, Molecular Cancer Therapeutics.

[6]  F. Stirpe,et al.  CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. , 1995, Blood.

[7]  C. Dumontet,et al.  Strategies and challenges for the next generation of antibody–drug conjugates , 2017, Nature Reviews Drug Discovery.

[8]  S. Bruno,et al.  CD85/LIR-1/ILT2 and CD152 (Cytotoxic T Lymphocyte Antigen 4) Inhibitory Molecules Down-Regulate the Cytolytic Activity of Human CD4+ T-Cell Clones Specific forMycobacterium tuberculosis , 2001, Infection and Immunity.

[9]  G. A. Lazar,et al.  A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens , 2011, mAbs.

[10]  J. Larkin,et al.  Management of toxicities of immune checkpoint inhibitors. , 2016, Cancer treatment reviews.

[11]  P. Kufer,et al.  Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. , 2006, Molecular immunology.

[12]  H. Sings,et al.  Review of vaccine effectiveness assumptions used in economic evaluations of infant pneumococcal conjugate vaccine , 2018, Expert review of vaccines.

[13]  Pamela A Shaw,et al.  Chimeric antigen receptor T cells for sustained remissions in leukemia. , 2014, The New England journal of medicine.

[14]  P. Buckley,et al.  Antibody-Based Biologics and Their Promise to Combat Staphylococcus aureus Infections. , 2016, Trends in pharmacological sciences.

[15]  D. Maloney,et al.  Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. , 2017, Blood.

[16]  D. J. Campbell Estimation of prevalence , 1984 .

[17]  N. F. Lima,et al.  Surface expression of inhibitory (CTLA-4) and stimulatory (OX40) receptors by CD4+ regulatory T cell subsets circulating in human malaria. , 2016, Microbes and infection.

[18]  G. Deepe,et al.  Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells , 2003, The Journal of experimental medicine.

[19]  J. Roszik,et al.  Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection , 2014, Proceedings of the National Academy of Sciences.

[20]  G. Freeman,et al.  Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation1 , 2009, The Journal of Immunology.

[21]  P. Boggiatto,et al.  Limitations of Foxp3(+) Treg depletion following viral infection in DEREG mice. , 2014, Journal of immunological methods.

[22]  Jérôme Cros,et al.  Targeting the TGFβ pathway for cancer therapy. , 2015, Pharmacology & therapeutics.

[23]  D. Thanassi,et al.  Bactericidal Action of a Complement-Independent Antibody against Relapsing Fever Borrelia Resides in Its Variable Region12 , 2008, The Journal of Immunology.

[24]  E. Jaffee,et al.  PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors , 2015, Journal of immunotherapy.

[25]  G. Freeman,et al.  PD-L2 is a second ligand for PD-1 and inhibits T cell activation , 2001, Nature Immunology.

[26]  S. Rosenberg,et al.  Adoptive immunotherapy for cancer: building on success , 2006, Nature Reviews Immunology.

[27]  A. Ali,et al.  scFv Antibody: Principles and Clinical Application , 2012, Clinical & developmental immunology.

[28]  L. Weiner,et al.  CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. , 2014, Blood.

[29]  G. Freeman,et al.  Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1) , 2013, Proceedings of the National Academy of Sciences.

[30]  R. Fischer,et al.  Microtubule-associated protein tau facilitates the targeted killing of proliferating cancer cells in vitro and in a xenograft mouse tumour model in vivo , 2013, British Journal of Cancer.

[31]  S. Lewin,et al.  Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. , 2015, AIDS.

[32]  G. Linette,et al.  CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges , 2018, Neuro-oncology.

[33]  C. Turtle,et al.  Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy. , 2018, Current research in translational medicine.

[34]  G. Plosker,et al.  Interferon Alfacon-1 , 2012, Drugs.

[35]  G. Zhu,et al.  Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. , 2005, Cancer research.

[36]  M. Ostrowski,et al.  TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection , 2016, PLoS pathogens.

[37]  A. Herrmann,et al.  Antagonistic TNF Receptor One-Specific Antibody (ATROSAB): Receptor Binding and In Vitro Bioactivity , 2013, PloS one.

[38]  R. Carlson,et al.  Chimeric Antigen Receptor T-Cell Therapy. , 2018, Journal of the National Comprehensive Cancer Network : JNCCN.

[39]  H. Nishida,et al.  Prevention of respiratory syncytial virus infections in high‐risk infantsby monoclonal antibody (palivizumab) , 2002, Pediatrics international : official journal of the Japan Pediatric Society.

[40]  R. Jain,et al.  Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery , 2015, Proceedings of the National Academy of Sciences.

[41]  Y. Li,et al.  Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis , 2015, Cancer immunology, immunotherapy : CII.

[42]  G. Schuler,et al.  Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer , 2009, Gene Therapy.

[43]  M. G. Jeppesen,et al.  Rationally designed chemokine-based toxin targeting the viral G protein-coupled receptor US28 potently inhibits cytomegalovirus infection in vivo , 2015, Proceedings of the National Academy of Sciences.

[44]  Louis M. Weiner,et al.  Antibody-Based Immunotherapy of Cancer , 2012, Cell.

[45]  I. Pastan,et al.  Chimeric toxins targeted to the human immunodeficiency virus type 1 envelope glycoprotein augment the in vivo activity of combination antiretroviral therapy in thy/liv-SCID-Hu mice. , 2000, The Journal of infectious diseases.

[46]  R. Ahmed,et al.  Features of responding T cells in cancer and chronic infection. , 2010, Current opinion in immunology.

[47]  P. Sharma,et al.  The future of immune checkpoint therapy , 2015, Science.

[48]  T. Graeber,et al.  Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. , 2016, The New England journal of medicine.

[49]  Mario Roederer,et al.  Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients , 1999, Nature Medicine.

[50]  S. Barth,et al.  Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells , 2018, Biomedicines.

[51]  N. Robert,et al.  Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. , 1997, Journal of Clinical Oncology.

[52]  N. Hahn,et al.  Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer , 2012, Human vaccines & immunotherapeutics.

[53]  T. Waldmann,et al.  Immunotherapy: past, present and future , 2003, Nature Medicine.

[54]  S. Kennel,et al.  Optimizations of Radiolabeling of Immunoproteins with 213Bi , 1997 .

[55]  J. Curtis,et al.  Early or Late IL-10 Blockade Enhances Th1 and Th17 Effector Responses and Promotes Fungal Clearance in Mice with Cryptococcal Lung Infection , 2014, The Journal of Immunology.

[56]  D. Pardoll,et al.  STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade , 2015, Science Translational Medicine.

[57]  Yang Zhang,et al.  Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward , 2018, Journal of Hematology & Oncology.

[58]  T. Sparwasser,et al.  Tregs in infection and vaccinology: heroes or traitors? , 2012, Microbial biotechnology.

[59]  H. Feng,et al.  Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B , 2014, Cell Research.

[60]  Thor A Wagner Quarter Century of Anti-HIV CAR T Cells , 2018, Current HIV/AIDS Reports.

[61]  G. Freeman,et al.  Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. , 2013, Cancer research.

[62]  World Health Organization Diphtheria vaccine: WHO position paper, August 2017 - Recommendations. , 2018, Vaccine.

[63]  S. Filler,et al.  NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. , 2012, Vaccine.

[64]  E. Wherry,et al.  Molecular and cellular insights into T cell exhaustion , 2015, Nature Reviews Immunology.

[65]  J. Blattman,et al.  Adoptive immunotherapy: engineering T cell responses as biologic weapons for tumor mass destruction. , 2003, Cancer cell.

[66]  Wenyan Zhong,et al.  Evolving Strategies for Target Selection for Antibody-Drug Conjugates , 2015, Pharmaceutical Research.

[67]  G. Weiner Building better monoclonal antibody-based therapeutics , 2015, Nature Reviews Cancer.

[68]  Jerome H. Kim,et al.  Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. , 2009, The New England journal of medicine.

[69]  L. Nguyen,et al.  Clinical blockade of PD1 and LAG3 — potential mechanisms of action , 2014, Nature Reviews Immunology.

[70]  M. Feldmann,et al.  Many cytokines are very useful therapeutic targets in disease. , 2008, The Journal of clinical investigation.

[71]  A. Casadevall,et al.  Targeted Killing of Virally Infected Cells by Radiolabeled Antibodies to Viral Proteins , 2006, PLoS medicine.

[72]  H. Liao,et al.  Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells. , 2015, The Journal of clinical investigation.

[73]  S. Lewin,et al.  Immune checkpoint blockade in infectious diseases , 2017, Nature Reviews Immunology.

[74]  X. Qu,et al.  New insights of CTLA-4 into its biological function in breast cancer. , 2010, Current cancer drug targets.

[75]  P. Marcellin,et al.  Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. , 2004, The New England journal of medicine.

[76]  M. Wei,et al.  Manipulating IL-10 signalling blockade for better immunotherapy. , 2015, Cellular immunology.

[77]  H. Einsele,et al.  Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody , 2008, Science.

[78]  J. Gartner,et al.  Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer , 2018, Nature Medicine.

[79]  Drew M. Pardoll,et al.  The blockade of immune checkpoints in cancer immunotherapy , 2012, Nature Reviews Cancer.

[80]  T. Yuraszeck,et al.  Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment , 2017, Clinical pharmacology and therapeutics.

[81]  A. Thakur,et al.  Bispecific antibody based therapeutics: Strengths and challenges. , 2018, Blood reviews.

[82]  Carlos Barrios,et al.  Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial , 2017, The Lancet.

[83]  S. Pittaluga,et al.  Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) , 2016, AIDS.

[84]  F. Kiessling,et al.  Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model. , 2016, Cancer letters.

[85]  Sergey E Sedykh,et al.  Bispecific antibodies: design, therapy, perspectives , 2018, Drug design, development and therapy.

[86]  J. Larkin,et al.  Pembrolizumab versus Ipilimumab in Advanced Melanoma. , 2015, The New England journal of medicine.

[87]  K. Steimer,et al.  Bispecific antibodies that mediate killing of cells infected with human immunodeficiency virus of any strain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[88]  O. Tsitsilonis,et al.  Harnessing the immune system to improve cancer therapy. , 2016, Annals of translational medicine.

[89]  Alimuddin Zumla,et al.  Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis , 2016, BMC Medicine.

[90]  J. Wolchok,et al.  Immune Checkpoint Blockade in Cancer Therapy. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[91]  S. Buchbinder,et al.  Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). , 2012, The Journal of infectious diseases.

[92]  F. Brombacher,et al.  Cytokine Therapy , 2005, Annals of the New York Academy of Sciences.

[93]  Q. Lu,et al.  Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia , 2014, European Journal of Clinical Microbiology and Infectious Diseases.

[94]  J. Soria,et al.  Immune-related adverse events with immune checkpoint blockade: a comprehensive review. , 2016, European journal of cancer.

[95]  Masami Watanabe,et al.  Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma , 2017, Oncotarget.

[96]  T. Wakabayashi,et al.  Cytokine therapy. , 2012, Advances in experimental medicine and biology.

[97]  Jinming Li,et al.  Bispecific antibodies and their applications , 2015, Journal of Hematology & Oncology.

[98]  G. Bancroft,et al.  Blockade of IL-10 Signaling during Bacillus Calmette-Guérin Vaccination Enhances and Sustains Th1, Th17, and Innate Lymphoid IFN-γ and IL-17 Responses and Increases Protection to Mycobacterium tuberculosis Infection , 2012, The Journal of Immunology.

[99]  A. Casadevall,et al.  Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole , 1993, Antimicrobial Agents and Chemotherapy.

[100]  S. Jakowlew Transforming growth factor-β in cancer and metastasis , 2006, Cancer and Metastasis Reviews.

[101]  L. Pirofski,et al.  Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide , 2003, Infection and Immunity.

[102]  Wei Zhang,et al.  Exosomal PD-L1 Contributes to Immunosuppression and is Associated with anti-PD-1 Response , 2018, Nature.

[103]  Wendell A Lim,et al.  Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities. , 2017, Annual review of immunology.

[104]  Herren Wu,et al.  Mechanisms of Neutralization of a Human Anti-α-toxin Antibody* , 2014, The Journal of Biological Chemistry.

[105]  A. Casadevall,et al.  Radiolabeled antibodies for therapy of infectious diseases. , 2014, Microbiology spectrum.

[106]  A. Ager,et al.  Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells , 2016, Biochemical Society transactions.

[107]  S. Kaufmann,et al.  Host-directed therapies for infectious diseases: current status, recent progress, and future prospects , 2016, The Lancet Infectious Diseases.

[108]  R. Fischer,et al.  Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B–Single-Chain Fv Fusion Protein , 2014, Antimicrobial Agents and Chemotherapy.

[109]  V. Golubovskaya,et al.  Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy , 2016, Cancers.

[110]  Protein engineering of diphtheria-toxin-related interleukin-2 fusion toxins to increase cytotoxic potency for high-affinity IL-2-receptor-bearing target cells. , 1991, Protein engineering.

[111]  M. Postow,et al.  Checkpoint blocking antibodies in cancer immunotherapy , 2014, FEBS letters.

[112]  L. Pirofski,et al.  Molecular and Functional Characteristics of a Protective Human Monoclonal Antibody to Serotype 8 Streptococcus pneumoniae Capsular Polysaccharide , 1999, Infection and Immunity.

[113]  A. Lesokhin,et al.  Immunotherapy , 2016, Advances in Experimental Medicine and Biology.

[114]  C. Cordon-Cardo,et al.  An α-Particle Emitting Antibody ([213Bi]J591) for Radioimmunotherapy of Prostate Cancer , 2000 .

[115]  I. Pastan,et al.  Anti‐HIV‐1 immunotoxin 3B3(Fv)‐PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques , 2006, Journal of leukocyte biology.

[116]  D. Barouch,et al.  New concepts in HIV-1 vaccine development. , 2016, Current opinion in immunology.

[117]  A. Casadevall,et al.  Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. , 1994, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[118]  L. Chappell,et al.  Delivery of the alpha-emitting radioisotope bismuth-213 to solid tumors via single-chain Fv and diabody molecules. , 2000, Nuclear medicine and biology.

[119]  S. Riddell,et al.  Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy , 2018, The Journal of Immunology.

[120]  Laurent Ducry,et al.  Antibody-Drug Conjugates , 2013, Methods in Molecular Biology.

[121]  K. Hess,et al.  Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[122]  R. Balderas,et al.  Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction , 2006, Nature Medicine.

[123]  A. Casadevall,et al.  Feasibility of Radioimmunotherapy of Experimental Pneumococcal Infection , 2004, Antimicrobial Agents and Chemotherapy.

[124]  M. Plebanski,et al.  Natural Regulatory T Cells and Persistent Viral Infection , 2007, Journal of Virology.

[125]  D. George An α‐Particle Emitting Antibody ([213Bi] J591) for Radioimmunotherapy of Prostate Cancer , 2001 .

[126]  K. Knutson,et al.  Accumulation of memory precursor CD8 T cells in regressing tumors following combination therapy with vaccine and anti-PD-1 antibody. , 2014, Cancer research.

[127]  D. Burton Antibodies, viruses and vaccines , 2002, Nature Reviews Immunology.

[128]  A. Oxenius,et al.  Macrophage and T Cell Produced IL-10 Promotes Viral Chronicity , 2013, PLoS pathogens.

[129]  L. Teyton,et al.  Interleukin-10 determines viral clearance or persistence in vivo , 2006, Nature Medicine.

[130]  Serge Muyldermans,et al.  Efficient tumor targeting by single‐domain antibody fragments of camels , 2002, International journal of cancer.

[131]  R. Derynck,et al.  Transforming growth factor‐α , 1990, Molecular reproduction and development.

[132]  G. Freeman,et al.  Restoring function in exhausted CD8 T cells during chronic viral infection , 2006, Nature.

[133]  Y. Erdi,et al.  Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[134]  H. Wang,et al.  Broad-spectrum antiviral agents , 2015, Front. Microbiol..

[135]  D. Ho,et al.  Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. , 1995, The New England journal of medicine.

[136]  Sergei A. Nedospasov,et al.  Prominent role for T cell-derived Tumour Necrosis Factor for sustained control of Mycobacterium tuberculosis infection , 2013, Scientific Reports.

[137]  R. Pazdur,et al.  FDA Approval: Blinatumomab , 2015, Clinical Cancer Research.

[138]  S. Nanjappa,et al.  Vaccine immunity against fungal infections. , 2014, Current opinion in immunology.

[139]  P. Kufer,et al.  BiTEs: bispecific antibody constructs with unique anti-tumor activity. , 2005, Drug discovery today.

[140]  I. Pastan,et al.  Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected Cell Reservoirs , 2010, PLoS pathogens.

[141]  A. Rieger,et al.  Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade. , 2017, Clinical immunology.

[142]  R. Charles Povey Persistent Viral Infection , 1986, Veterinary Clinics of North America: Small Animal Practice.

[143]  J. Obrecht [Cancer therapy]. , 1977, Deutsche medizinische Wochenschrift.

[144]  M. Chambers,et al.  Form and function : an introduction to the TB granuloma and granuloma pathogenesis , 2016 .

[145]  T. Sparwasser,et al.  Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points , 2011, Proceedings of the National Academy of Sciences.

[146]  T. Knösel,et al.  Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab , 2015, Journal of Hematology & Oncology.

[147]  C. Horak,et al.  Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. , 2016, The Lancet. Oncology.

[148]  Martine De Vos,et al.  Generation and Characterization of Small Single Domain Antibodies Inhibiting Human Tumor Necrosis Factor Receptor 1* , 2014, The Journal of Biological Chemistry.

[149]  G. Brede,et al.  Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination , 2018, Front. Immunol..

[150]  A. Rudensky,et al.  Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice , 2007, Nature Immunology.

[151]  Ana C Anderson,et al.  Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. , 2016, Immunity.

[152]  B. Foxwell,et al.  Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. , 2008, Rheumatology.

[153]  T. Chittenden,et al.  Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. , 2006, Cancer research.

[154]  T. Gajewski,et al.  Cancer immunotherapy , 2012, Molecular oncology.

[155]  P. Desai,et al.  Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2 , 2014, Antimicrobial Agents and Chemotherapy.

[156]  Marla Shapiro,et al.  Understanding modern-day vaccines: what you need to know , 2018, Annals of medicine.

[157]  A. Casadevall,et al.  Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[158]  P. Moore,et al.  Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells , 2015, PLoS pathogens.

[159]  P. Dijke,et al.  TGF-β signalling and its role in cancer progression and metastasis , 2012, Cancer and Metastasis Reviews.

[160]  N. Mohindra Current state of immunotherapy: chipping away at the tip of the iceberg. , 2018 .

[161]  R. Verma,et al.  Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapy , 2009, Cancer science.

[162]  D. McGavern,et al.  Therapeutic Blockade of Transforming Growth Factor Beta Fails To Promote Clearance of a Persistent Viral Infection , 2012, Journal of Virology.

[163]  G. Schmidt,et al.  Bacterial Toxins for Cancer Therapy , 2017, Toxins.

[164]  T. Graeber,et al.  Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. , 2017, Cancer discovery.

[165]  F. Stossi,et al.  A Homing System Targets Therapeutic T-cells to Brain Cancer , 2018, Nature.

[166]  S. Rosenberg,et al.  Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors , 2013, Nature Reviews Clinical Oncology.

[167]  Stephen J. Schuster,et al.  Chimeric Antigen Receptor T Cells in Refractory B‐Cell Lymphomas , 2017, The New England journal of medicine.

[168]  J. Agrewala,et al.  T-cell exhaustion in tuberculosis: pitfalls and prospects , 2017, Critical reviews in microbiology.

[169]  Jiunn H. Lin,et al.  Challenges of Antibody Drug Conjugates in Cancer Therapy: Current Understanding of Mechanisms and Future Strategies , 2018, Current Pharmacology Reports.

[170]  World Health Organization Measles vaccines: WHO position paper, April 2017 - Recommendations. , 2019, Vaccine.

[171]  W. Han,et al.  Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV , 2017, Protein & Cell.

[172]  O. Ahmadpour,et al.  Human leukocyte derived interferon-alpha in a hydrophilic gel for the treatment of intravaginal warts in women: a placebo-controlled, double-blind study , 1998, International journal of STD & AIDS.

[173]  S. Sadekar,et al.  Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection , 2015, The AAPS Journal.

[174]  P. Greenberg,et al.  Tolerance and exhaustion: defining mechanisms of T cell dysfunction. , 2014, Trends in immunology.

[175]  B. Allen Can α-radioimmunotherapy increase efficacy for the systemic control of cancer? , 2011, Immunotherapy.

[176]  M. Netea,et al.  Immunotherapeutic approaches to treatment of fungal diseases. , 2017, The Lancet. Infectious diseases.

[177]  Emily B Hanhauser,et al.  Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30 , 2018, PLoS pathogens.

[178]  L. Iamele,et al.  Antibody–drug conjugates: targeted weapons against cancer , 2015 .

[179]  C. Loddenkemper,et al.  Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease , 2007, The Journal of experimental medicine.

[180]  G. Freeman,et al.  The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection , 2007, Nature Immunology.

[181]  H. Mollenkopf,et al.  Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis. , 2014, American journal of respiratory and critical care medicine.

[182]  T. Curiel,et al.  IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. , 2007, Blood.

[183]  Kole T. Roybal,et al.  Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors , 2016, Cell.

[184]  J. Remacle,et al.  CTLA‐4 interacts with STAT5 and inhibits STAT5‐mediated transcription , 2006, Immunology.

[185]  Y. Okuno,et al.  An IL‐27/Stat3 axis induces expression of programmed cell death 1 ligands (PD‐L1/2) on infiltrating macrophages in lymphoma , 2016, Cancer science.

[186]  B. Moss,et al.  Anti-HIV activity of CD4-Pseudomonas exotoxin on infected primary human lymphocytes and monocyte/macrophages. , 1991, The Journal of infectious diseases.

[187]  E. Wherry,et al.  Overcoming T cell exhaustion in infection and cancer. , 2015, Trends in immunology.

[188]  F. Chisari,et al.  Immunobiology and pathogenesis of viral hepatitis. , 2006, Annual review of pathology.

[189]  R. Coffman,et al.  Interleukin-10 (IL-10) in Experimental Visceral Leishmaniasis and IL-10 Receptor Blockade as Immunotherapy , 2002, Infection and Immunity.

[190]  S. Muyldermans,et al.  Naturally occurring antibodies devoid of light chains , 1993, Nature.

[191]  H. Lutz,et al.  Naturally occurring antibodies. , 2012, Advances in experimental medicine and biology.

[192]  J. Suzich,et al.  Assessment of an Anti-Alpha-Toxin Monoclonal Antibody for Prevention and Treatment of Staphylococcus aureus-Induced Pneumonia , 2013, Antimicrobial Agents and Chemotherapy.

[193]  Yíngyún Caì,et al.  An immunotoxin targeting the gH glycoprotein of KSHV for selective killing of cells in the lytic phase of infection. , 2011, Antiviral research.

[194]  Jennifer Kleponis,et al.  Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors , 2015, Cancer biology & medicine.

[195]  M. Kamata,et al.  Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS , 2017, PLoS pathogens.

[196]  H. Larson,et al.  Measuring trust in vaccination: A systematic review , 2018, Human vaccines & immunotherapeutics.

[197]  W. Bishai,et al.  Suppressor Cell–Depleting Immunotherapy With Denileukin Diftitox is an Effective Host-Directed Therapy for Tuberculosis , 2017, The Journal of infectious diseases.

[198]  K. Lennert,et al.  The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. , 1985, Blood.

[199]  Eugene A Zhukovsky,et al.  Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection. , 2016, Current opinion in immunology.

[200]  J. Carlis,et al.  Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. , 2011, The Journal of clinical investigation.

[201]  B. Chandran,et al.  Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein , 2012, mAbs.

[202]  T. Yuraszeck,et al.  Immunotherapy and Novel Combinations in Oncology: Current Landscape, Challenges, and Opportunities , 2016, Clinical and translational science.

[203]  P. S. Andersen,et al.  Novel antibody–antibiotic conjugate eliminates intracellular S. aureus , 2015, Nature.

[204]  D. Seimetz,et al.  Catumaxomab , 2010, mAbs.

[205]  J. Bubeck Wardenburg,et al.  Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue , 2013, Toxins.

[206]  S. Barth,et al.  Human MAP Tau Based Targeted Cytolytic Fusion Proteins , 2017, Biomedicines.

[207]  Michel Sadelain,et al.  Targeting tumours with genetically enhanced T lymphocytes , 2003, Nature Reviews Cancer.

[208]  N. Becker,et al.  Antibody-Based Immunotoxins for the Treatment of Cancer , 2012 .

[209]  G. Linette,et al.  Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. , 2016, The Lancet. Oncology.

[210]  Measles vaccines: WHO position paper. , 2009, Releve epidemiologique hebdomadaire.

[211]  E. Rosenberg,et al.  Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction , 2007, Nature Immunology.

[212]  B. Graham,et al.  History of passive antibody administration for prevention and treatment of infectious diseases , 2015, Current opinion in HIV and AIDS.

[213]  P. Kufer,et al.  Antiviral Activity of HIV gp120-Targeting Bispecific T Cell Engager Antibody Constructs , 2018, Journal of Virology.

[214]  M. Rosenkilde,et al.  The future of antiviral immunotoxins , 2016, Journal of leukocyte biology.

[215]  D. Raulet,et al.  Cytokine therapy restores antitumor responses of NK cells rendered anergic in MHC I-deficient tumors , 2016, Oncoimmunology.

[216]  Loise M. Francisco,et al.  PD-L1 regulates the development, maintenance, and function of induced regulatory T cells , 2009, The Journal of experimental medicine.

[217]  R. Koup,et al.  Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy , 2017, The Journal of infectious diseases.

[218]  D. Douek,et al.  Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection , 2010, Nature Medicine.

[219]  D. Maloney,et al.  Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. , 2017, Blood.

[220]  G. Bancroft,et al.  Blockade of IL-10 signaling during BCG vaccination enhances and sustains Th 1 , Th 17 , and innate lymphoid IFN-γ and IL-17 responses and increases protection to Mycobacterium tuberculosis infection , 2012 .

[221]  R. Ahmed,et al.  Programmed cell death 1-directed immunotherapy for enhancing T-cell function. , 2013, Cold Spring Harbor symposia on quantitative biology.

[222]  Eunhee Kim,et al.  Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics , 2015, Biomolecules & therapeutics.

[223]  P. Trail,et al.  Antibody drug conjugates for treatment of breast cancer: Novel targets and diverse approaches in ADC design. , 2018, Pharmacology & therapeutics.

[224]  R. Bourgon,et al.  Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial , 2017, The Lancet.

[225]  Joan L. Robinson,et al.  Treatment of respiratory syncytial virus with palivizumab: a systematic review , 2010, World journal of pediatrics : WJP.

[226]  F. Hsu,et al.  A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma , 2017, Journal of immunology research.

[227]  有馬 俊六郎,et al.  生乳のStaphylococcus aureus (α-toxin)発育抑制作用について.I. , 1958 .

[228]  Peter D. Crompton,et al.  Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion , 2013, The Journal of Immunology.

[229]  G. Efimov,et al.  Making anti‐cytokine therapy more selective: Studies in mice , 2018, Cytokine.

[230]  Avner Friedman,et al.  Combination therapy of cancer with cancer vaccine and immune checkpoint inhibitors: A mathematical model , 2017, PloS one.

[231]  Hao Liu,et al.  CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. , 2011, The Journal of clinical investigation.

[232]  R. Advani,et al.  Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. , 2018, Blood.

[233]  G. Coukos,et al.  Phage antibody display libraries: a powerful antibody discovery platform for immunotherapy , 2016, Critical reviews in biotechnology.

[234]  L. Dyck,et al.  Immune checkpoints and their inhibition in cancer and infectious diseases , 2017, European journal of immunology.

[235]  J. Dutcher Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. , 2002, Oncology.

[236]  Burton E. Barnett,et al.  Progenitor and Terminal Subsets of CD8+ T Cells Cooperate to Contain Chronic Viral Infection , 2012, Science.

[237]  Inger Sandlie,et al.  Therapeutic antibodies for human diseases at the dawn of the twenty-first century , 2003, Nature Reviews Drug Discovery.

[238]  P. Wentworth,et al.  Investigating antibody-catalyzed ozone generation by human neutrophils , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[239]  P. T. Jones,et al.  Replacing the complementarity-determining regions in a human antibody with those from a mouse , 1986, Nature.

[240]  I. Navarro-Teulon,et al.  Clinical radioimmunotherapy—the role of radiobiology , 2011, Nature Reviews Clinical Oncology.

[241]  K. Reddy,et al.  A Randomized, Double-Blind, Placebo-Controlled Assessment of BMS-936558, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients with Chronic Hepatitis C Virus Infection , 2013, PloS one.

[242]  S. Kaufmann,et al.  Cutting Edge: Regulatory T Cells Prevent Efficient Clearance of Mycobacterium tuberculosis , 2007, The Journal of Immunology.

[243]  S. Gordon,et al.  Cell-type–restricted anti-cytokine therapy: TNF inhibition from one pathogenic source , 2016, Proceedings of the National Academy of Sciences.

[244]  S. Mariathasan,et al.  Antibody-Antibiotic Conjugates: A Novel Therapeutic Platform against Bacterial Infections. , 2017, Trends in molecular medicine.

[245]  C. Marano,et al.  The immunogenicity and safety of GSK’s recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience , 2017, Expert review of vaccines.

[246]  S. Narula,et al.  From cloning to a commercial realization: human alpha interferon. , 1990, Critical reviews in biotechnology.

[247]  M. Fanger,et al.  Bispecific antibodies. , 1992, Critical reviews in immunology.

[248]  D. Burton,et al.  Passive immunotherapy of viral infections: 'super-antibodies' enter the fray , 2018, Nature Reviews Immunology.

[249]  M. V. von Herrath,et al.  TGF-β blockade does not improve control of an established persistent viral infection. , 2012, Viral immunology.

[250]  R. Frazzi,et al.  In vitro Activity of Monoclonal and Recombinant Yeast Killer Toxin-like Antibodies Against Antibiotic-resistant Gram-positive Cocci , 2000, Molecular medicine.

[251]  J. Miller,et al.  Heterodimeric Bispecific Single Chain Variable Fragments (scFv) Killer Engagers (BiKEs) Enhance NK-cell Activity Against CD133+ Colorectal Cancer Cells , 2016, Targeted Oncology.

[252]  W. Schiemann,et al.  Transforming growth factor-β and the hallmarks of cancer. , 2011, Cellular signalling.

[253]  E. Chiang,et al.  TIGIT: A Key Inhibitor of the Cancer Immunity Cycle. , 2017, Trends in immunology.

[254]  C. Drake,et al.  Immune checkpoint blockade: a common denominator approach to cancer therapy. , 2015, Cancer cell.

[255]  S L Morrison,et al.  Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[256]  C. Horak,et al.  Nivolumab plus ipilimumab in advanced melanoma. , 2013, The New England journal of medicine.

[257]  B. Ryffel,et al.  Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects. , 2005, Immunity.

[258]  D. Burton,et al.  The antiviral activity of antibodies in vitro and in vivo , 2001, Advances in Immunology.

[259]  Distinct advancements and challenges in HIV 1 vaccine development and cure—A review , 2014 .

[260]  E. Winer,et al.  Atezolizumab and Nab‐Paclitaxel in Advanced Triple‐Negative Breast Cancer , 2018, The New England journal of medicine.

[261]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[262]  J. Marks,et al.  Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV. , 2002, The Journal of infectious diseases.

[263]  Martin A. Cheever,et al.  PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine , 2011, Clinical Cancer Research.

[264]  E John Wherry,et al.  Molecular and transcriptional basis of CD4⁺ T cell dysfunction during chronic infection. , 2014, Immunity.

[265]  C. Karp,et al.  Therapeutic Enhancement of Protective Immunity during Experimental Leishmaniasis , 2011, PLoS neglected tropical diseases.

[266]  R. Levy,et al.  Axicabtagene Ciloleucel CAR T‐Cell Therapy in Refractory Large B‐Cell Lymphoma , 2017, The New England journal of medicine.

[267]  M. Amacker,et al.  A virosomal vaccine against candidal vaginitis: immunogenicity, efficacy and safety profile in animal models. , 2012, Vaccine.

[268]  J. Church Upregulation of PD-1 Expression on HIV-Specific CD8+ T Cells Leads to Reversible Immune Dysfunction , 2007, Pediatrics.

[269]  J. Esparza,et al.  More Surprises in the Development of an HIV Vaccine , 2014, Front. Immunol..

[270]  Xue-jun Fan,et al.  Targeting Human-Cytomegalovirus-Infected Cells by Redirecting T Cells Using an Anti-CD3/Anti-Glycoprotein B Bispecific Antibody , 2017, Antimicrobial Agents and Chemotherapy.

[271]  W. Haining,et al.  Resolution of a chronic viral infection after interleukin-10 receptor blockade , 2006, The Journal of experimental medicine.

[272]  S. J. Schrieber,et al.  FDA Approval: Ado-Trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer , 2014, Clinical Cancer Research.

[273]  S. Rosenberg,et al.  High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[274]  S. Nedospasov,et al.  Pathogenic and Protective Functions of TNF in Neuroinflammation Are Defined by Its Expression in T Lymphocytes and Myeloid Cells , 2011, The Journal of Immunology.

[275]  D. Schadendorf,et al.  Nivolumab in previously untreated melanoma without BRAF mutation. , 2015, The New England journal of medicine.

[276]  J. Lessler,et al.  Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis , 2017, The Lancet. Infectious diseases.

[277]  G. Nabel Designing tomorrow's vaccines. , 2013, The New England journal of medicine.

[278]  K. Karjalainen,et al.  Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes , 1995, The Journal of experimental medicine.

[279]  B. Haynes New approaches to HIV vaccine development. , 2015, Current opinion in immunology.

[280]  T. Illidge,et al.  The Emerging Role Of Radioimmunotherapy In Haematological Malignancies , 2000, British journal of haematology.

[281]  G. Anderson,et al.  Trans-Endocytosis of CD80 and CD86: A Molecular Basis for the Cell-Extrinsic Function of CTLA-4 , 2011, Science.

[282]  T. Chou,et al.  Immunotherapy of cancer. , 1970, British medical journal.

[283]  T. Curiel,et al.  Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[284]  T. Allen Ligand-targeted therapeutics in anticancer therapy , 2002, Nature Reviews Cancer.

[285]  A. Zuercher,et al.  Preclinical In Vitro and In Vivo Characterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific for Pseudomonas aeruginosa Serotype IATS-O11 , 2010, Antimicrobial Agents and Chemotherapy.

[286]  D. Fuchs,et al.  Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection1 , 2008, The Journal of Immunology.

[287]  E. Wherry,et al.  The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responses. , 2009, Current opinion in immunology.

[288]  W. Xie,et al.  Enrichment of regulatory T-cells in blood of patients with multidrug-resistant tuberculosis. , 2015, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.