Nanoparticle-based immunotherapy for cancer.

The design of nanovaccines capable of triggering effective antitumor immunity requires an understanding of how the immune system senses and responds to threats, including pathogens and tumors. Equally important is an understanding of the mechanisms employed by tumor cells to evade immunity and an appreciation of the deleterious effects that antitumor immune responses can have on tumor growth, such as by skewing tumor cell composition toward immunologically silent tumor cell variants. The immune system and tumors engage in a tug-of-war driven by competition where promoting antitumor immunity or tumor cell death alone may be therapeutically insufficient. Nanotechnology affords a unique opportunity to develop therapeutic compounds than can simultaneously tackle both aspects, favoring tumor eradication. Here, we review the current status of nanoparticle-based immunotherapeutic strategies for the treatment of cancer, ranging from antigen/adjuvant delivery vehicles (to professional antigen-presenting cell types of the immune system) to direct tumor antigen-specific T-lymphocyte-targeting compounds and their combinations thereof.

[1]  A. Gabizon,et al.  Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Saconato,et al.  Comparative incidence of cancer in HIV-AIDS patients and transplant recipients. , 2012, Cancer epidemiology.

[3]  K. Rock,et al.  Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity , 1995, Nature Medicine.

[4]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[5]  D. Heymann,et al.  Mifamurtide for the treatment of nonmetastatic osteosarcoma , 2011, Expert opinion on pharmacotherapy.

[6]  S. Nie,et al.  Therapeutic Nanoparticles for Drug Delivery in Cancer Types of Nanoparticles Used as Drug Delivery Systems , 2022 .

[7]  S. Ren,et al.  Smart nanodevice combined tumor-specific vector with cellular microenvironment-triggered property for highly effective antiglioma therapy. , 2014, ACS nano.

[8]  Pau Serra,et al.  Reversal of autoimmunity by boosting memory-like autoregulatory T cells. , 2010, Immunity.

[9]  A. Hill,et al.  Small Cationic DDA:TDB Liposomes as Protein Vaccine Adjuvants Obviate the Need for TLR Agonists in Inducing Cellular and Humoral Responses , 2012, PloS one.

[10]  G. Keating,et al.  Polyethylene glycol-liposomal doxorubicin: a review of its use in the management of solid and haematological malignancies and AIDS-related Kaposi's sarcoma. , 2002, Drugs.

[11]  Alberto Mantovani,et al.  Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. , 2006, European journal of cancer.

[12]  Warren C W Chan,et al.  Nanoparticle-mediated cellular response is size-dependent. , 2008, Nature nanotechnology.

[13]  D. Gabrilovich Mechanisms and functional significance of tumour-induced dendritic-cell defects , 2004, Nature Reviews Immunology.

[14]  T. Fahmy,et al.  A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[15]  D. Irvine,et al.  Induction of potent anti-tumor responses while eliminating systemic side effects via liposome-anchored combinatorial immunotherapy. , 2011, Biomaterials.

[16]  Wei Lu,et al.  Targeted Photothermal Ablation of Murine Melanomas with Melanocyte-Stimulating Hormone Analog–Conjugated Hollow Gold Nanospheres , 2009, Clinical Cancer Research.

[17]  R. Herbst,et al.  B7-H1/PD-1 Blockade Therapy in Non–Small Cell Lung Cancer: Current Status and Future Direction , 2014, Cancer journal.

[18]  Shyh-Dar Li,et al.  A docetaxel-carboxymethylcellulose nanoparticle outperforms the approved taxane nanoformulation, Abraxane, in mouse tumor models with significant control of metastases. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[19]  Jie Li,et al.  Size-Dependent Immunogenicity: Therapeutic and Protective Properties of Nano-Vaccines against Tumors1 , 2004, The Journal of Immunology.

[20]  Lu Zhang,et al.  Intravenous delivery of siRNA targeting CD47 effectively inhibits melanoma tumor growth and lung metastasis. , 2013, Molecular therapy : the journal of the American Society of Gene Therapy.

[21]  R. Steinman,et al.  Antibody to Langerin/CD207 localizes large numbers of CD8α+ dendritic cells to the marginal zone of mouse spleen , 2009, Proceedings of the National Academy of Sciences.

[22]  S. Quezada,et al.  Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. , 2006, Current opinion in immunology.

[23]  M. Edidin,et al.  Nanoscale artificial antigen presenting cells for T cell immunotherapy. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[24]  G. Schackert,et al.  Tumor Evasion from T Cell Surveillance , 2011, Journal of biomedicine & biotechnology.

[25]  C. June,et al.  HLA tetramer-based artificial antigen-presenting cells for stimulation of CD4+ T cells. , 2003, Clinical immunology.

[26]  Peisheng Zhang,et al.  Induction of postsurgical tumor immunity and T-cell memory by a poorly immunogenic tumor. , 2007, Cancer research.

[27]  R. Schreiber,et al.  Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion , 2011, Science.

[28]  A. Eggermont Therapeutic vaccines in solid tumours: can they be harmful? , 2009, European journal of cancer.

[29]  Kinam Park,et al.  Targeted drug delivery to tumors: myths, reality and possibility. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[30]  Tarek R. Fadel,et al.  An Artificial Antigen-presenting Cell with Paracrine Delivery of IL-2 Impacts the Magnitude and Direction of the T Cell Response* , 2011, The Journal of Biological Chemistry.

[31]  Jlenia Guarnerio,et al.  Synthetic CD4+ T cell-targeted antigen-presenting cells elicit protective antitumor responses. , 2008, Cancer research.

[32]  Chen Jiang,et al.  T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting. , 2013, International journal of pharmaceutics.

[33]  K. Greish,et al.  Anticancer nanomedicine and tumor vascular permeability; Where is the missing link? , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Michael Dougan,et al.  Immune therapy for cancer. , 2009, Annual review of immunology.

[35]  M. Bianchi Killing cancer cells, twice with one shot , 2013, Cell Death and Differentiation.

[36]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[37]  R. Jain,et al.  Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. , 2013, Cancer research.

[38]  R. P. Andres,et al.  Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. , 2006, Bioconjugate chemistry.

[39]  Yang Yang,et al.  Peptide-MHC-based nanovaccines for the treatment of autoimmunity: a “one size fits all” approach? , 2011, Journal of Molecular Medicine.

[40]  P. Coulie,et al.  Tumor-Specific Antigens and Immunologic Adjuvants in Cancer Immunotherapy , 2011, Cancer journal.

[41]  F. di Costanzo,et al.  Oncotargets and Therapy Dovepress Open Access to Scientific and Medical Research Open Access Full Text Article Dovepress Targeted Delivery of Albumin Bound Paclitaxel in the Treatment of Advanced Breast Cancer , 2022 .

[42]  Y. Pei,et al.  Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[43]  Christine Allen,et al.  The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles. , 2010, Molecular pharmaceutics.

[44]  S. Rosenberg,et al.  Cancer immunotherapy: moving beyond current vaccines , 2004, Nature Medicine.

[45]  J. Hubbell,et al.  Enhancing Efficacy of Anticancer Vaccines by Targeted Delivery to Tumor-Draining Lymph Nodes , 2014, Cancer Immunology Research.

[46]  Young Keun Kim,et al.  A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy. , 2011, Nature nanotechnology.

[47]  M. Flattery Incidence and treatment of cancer in transplant recipients. , 1998, Journal of transplant coordination : official publication of the North American Transplant Coordinators Organization.

[48]  Katrin Schwarz,et al.  Nanoparticles target distinct dendritic cell populations according to their size , 2008, European journal of immunology.

[49]  J. Wolchok,et al.  Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma , 2013, The Journal of experimental medicine.

[50]  Min Beom Heo,et al.  Polymer nanoparticles for enhanced immune response: combined delivery of tumor antigen and small interference RNA for immunosuppressive gene to dendritic cells. , 2014, Acta biomaterialia.

[51]  P. Stayton,et al.  pH-Responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. , 2013, ACS nano.

[52]  Jennifer A. McWilliams,et al.  Relating TCR-peptide-MHC affinity to immunogenicity for the design of tumor vaccines. , 2006, The Journal of clinical investigation.

[53]  Thierry Boon,et al.  Human T cell responses against melanoma. , 2006, Annual review of immunology.

[54]  S. Dow,et al.  Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes1 , 2006, The Journal of Immunology.

[55]  Ru Cheng,et al.  pH-sensitive polymeric nanoparticles for tumor-targeting doxorubicin delivery: concept and recent advances. , 2014, Nanomedicine.

[56]  M. Akashi,et al.  Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity1 , 2007, The Journal of Immunology.

[57]  A. Ashkenazi,et al.  Targeting death and decoy receptors of the tumour-necrosis factor superfamily , 2002, Nature Reviews Cancer.

[58]  Shawn C. Owen,et al.  Stability of Self-Assembled Polymeric Micelles in Serum , 2011, Macromolecules.

[59]  Yuhua Wang,et al.  Nanoparticle-Delivered Transforming Growth Factor-β siRNA Enhances Vaccination against Advanced Melanoma by Modifying Tumor Microenvironment , 2014, ACS nano.

[60]  V. Torchilin,et al.  Multifunctional polymeric micelles for delivery of drugs and siRNA , 2014, Front. Pharmacol..

[61]  M. Raffeld,et al.  Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes , 2002, Science.

[62]  C. Meijer,et al.  Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system? , 2002, Blood.

[63]  J. Richie,et al.  Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[64]  S. Rosenberg,et al.  Adoptive cell transfer: a clinical path to effective cancer immunotherapy , 2008, Nature Reviews Cancer.

[65]  L. Kwak,et al.  The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1/Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma. , 2014, Biomaterials.

[66]  G. Trinchieri,et al.  Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti–Interleukin 10 Receptor Antibody , 2002, The Journal of experimental medicine.

[67]  A. Cochran,et al.  Sentinel Lymph Nodes Show Profound Downregulation of Antigen-Presenting Cells of the Paracortex: Implications for Tumor Biology and Treatment , 2001, Modern Pathology.

[68]  Min Beom Heo,et al.  Programmed nanoparticles for combined immunomodulation, antigen presentation and tracking of immunotherapeutic cells. , 2014, Biomaterials.

[69]  Marina A Dobrovolskaia,et al.  Nanoparticles and the immune system. , 2010, Endocrinology.

[70]  B. Baban,et al.  Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. , 2004, The Journal of clinical investigation.

[71]  P. Kantoff,et al.  Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  S. Fuchs,et al.  Targeting CpG Oligonucleotides to the Lymph Node by Nanoparticles Elicits Efficient Antitumoral Immunity1 , 2008, The Journal of Immunology.

[73]  W. Jiskoot,et al.  Co-encapsulation of antigen and Toll-like receptor ligand in cationic liposomes affects the quality of the immune response in mice after intradermal vaccination. , 2011, Vaccine.

[74]  G. Parmiani,et al.  A listing of human tumor antigens recognized by T cells: March 2004 update , 2005, Cancer Immunology, Immunotherapy.

[75]  Yuhua Wang,et al.  Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[76]  Sebastian Amigorena,et al.  In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor , 2007 .

[77]  R. Edwards,et al.  Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. , 2011, Blood.

[78]  G. Hur,et al.  The Immune Tolerance of Cancer is Mediated by IDO That is Inhibited by COX-2 Inhibitors Through Regulatory T Cells , 2009, Journal of immunotherapy.

[79]  R. Offringa,et al.  Activation of Dendritic Cells That Cross-Present Tumor-Derived Antigen Licenses CD8+ CTL to Cause Tumor Eradication1 , 2004, The Journal of Immunology.

[80]  Mauro Ferrari,et al.  Intravascular Delivery of Particulate Systems: Does Geometry Really Matter? , 2008, Pharmaceutical Research.

[81]  R. Schreiber,et al.  Natural innate and adaptive immunity to cancer. , 2011, Annual review of immunology.

[82]  B. Frisch,et al.  Targeted Delivery of α-Galactosylceramide to CD8α+ Dendritic Cells Optimizes Type I NKT Cell–Based Antitumor Responses , 2014, The Journal of Immunology.

[83]  G. Hartmann,et al.  Delivery by Cationic Gelatin Nanoparticles Strongly Increases the Immunostimulatory Effects of CpG Oligonucleotides , 2008, Pharmaceutical Research.

[84]  Sai T Reddy,et al.  Exploiting lymphatic transport and complement activation in nanoparticle vaccines , 2007, Nature Biotechnology.

[85]  Rishi Shanker,et al.  Impact of nanoparticles on the immune system. , 2011, Journal of biomedical nanotechnology.

[86]  G. Ogg,et al.  Ex Vivo Staining of Metastatic Lymph Nodes by Class I Major Histocompatibility Complex Tetramers Reveals High Numbers of Antigen-experienced Tumor-specific Cytolytic T Lymphocytes , 1998, The Journal of experimental medicine.

[87]  Vladimir Torchilin,et al.  Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance , 2012, Clinical Cancer Research.

[88]  R K Jain,et al.  Openings between defective endothelial cells explain tumor vessel leakiness. , 2000, The American journal of pathology.

[89]  C. Craik,et al.  Inhibition of Granzyme B by PI‐9 protects prostate cancer cells from apoptosis , 2012, The Prostate.

[90]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[91]  Ruslan Medzhitov,et al.  Toll Pathway-Dependent Blockade of CD4+CD25+ T Cell-Mediated Suppression by Dendritic Cells , 2003, Science.

[92]  D. Schadendorf,et al.  Improved survival with ipilimumab in patients with metastatic melanoma. , 2010, The New England journal of medicine.

[93]  A. Mackensen,et al.  Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig–coated artificial antigen-presenting cells , 2003, Nature Medicine.

[94]  Nathalie Vigneron,et al.  Database of T cell-defined human tumor antigens: the 2013 update. , 2013, Cancer immunity.

[95]  Simone Mocellin,et al.  Part I: Vaccines for solid tumours. , 2004, The Lancet. Oncology.

[96]  S. Ugel,et al.  In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer. , 2009, Cancer research.

[97]  Ronnie H. Fang,et al.  Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery , 2014, Nano letters.

[98]  George Coukos,et al.  Cancer immunotherapy comes of age , 2011, Nature.

[99]  Z. Trajanoski,et al.  Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome , 2006, Science.

[100]  John Steel,et al.  Programming the magnitude and persistence of antibody responses with innate immunity , 2010, Nature.

[101]  T. Curiel,et al.  Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunity , 2003, Nature Medicine.

[102]  D. Munn,et al.  The tumor‐draining lymph node as an immune‐privileged site , 2006, Immunological reviews.

[103]  Liangfang Zhang,et al.  Nanoparticle approaches against bacterial infections. , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[104]  B. Pockaj,et al.  Cyclooxygenase-2 Inhibitor Enhances the Efficacy of a Breast Cancer Vaccine: Role of IDO1 , 2006, The Journal of Immunology.

[105]  P. Robbins,et al.  A listing of human tumor antigens recognized by T cells , 2001, Cancer Immunology, Immunotherapy.

[106]  Nicolas Bertrand,et al.  The journey of a drug-carrier in the body: an anatomo-physiological perspective. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[107]  H. Schreiber,et al.  Innate and adaptive immune cells in the tumor microenvironment , 2013, Nature Immunology.

[108]  Mark E. Davis,et al.  Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. , 2003, Bioconjugate chemistry.

[109]  R. Vile,et al.  Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[110]  D. Mooney,et al.  In Vivo Modulation of Dendritic Cells by Engineered Materials: Towards New Cancer Vaccines. , 2011, Nano today.

[111]  J. A. Lopez,et al.  Dendritic cell dysfunction in cancer: A mechanism for immunosuppression , 2005, Immunology and cell biology.

[112]  L. Zitvogel,et al.  Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[113]  F. Meng,et al.  Latex bead-based artificial antigen-presenting cells induce tumor-specific CTL responses in the native T-cell repertoires and inhibit tumor growth. , 2013, Immunology letters.

[114]  Feng Gao,et al.  In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. , 2010, ACS nano.

[115]  M. Ernstoff,et al.  Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma. , 2011, The Journal of clinical investigation.

[116]  David Leong,et al.  Type 1 and 2 immunity following vaccination is influenced by nanoparticle size: formulation of a model vaccine for respiratory syncytial virus. , 2007, Molecular pharmaceutics.

[117]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[118]  F. B. Bombelli,et al.  The scope of nanoparticle therapies for future metastatic melanoma treatment. , 2014, The Lancet. Oncology.

[119]  H. V. van Boven,et al.  Overall survival and PD‐L1 expression in metastasized malignant melanoma , 2011, Cancer.

[120]  K. Ishii,et al.  RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma. , 2014, Cancer research.

[121]  T. Kaisho,et al.  Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction , 2013, The Journal of Immunology.

[122]  Y. Barenholz,et al.  Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. , 1994, Cancer research.

[123]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[124]  T. Eberlein gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma , 2012 .

[125]  J. Hubbell,et al.  Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response. , 2014, Biomaterials.

[126]  B. Thompson,et al.  F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. , 2012, Immunity.

[127]  Krishnendu Roy,et al.  Micro and Nanoparticle‐Based Delivery Systems for Vaccine Immunotherapy: An Immunological and Materials Perspective , 2013, Advanced healthcare materials.