Laser assisted immunotherapy (LIT) for chemotherapy-resistant neoplasms: recent case reports

T-cell stimulators such as anti-CTLA-4 antibodies enhance immunologic responses to chemotherapy-resistant solid tumors, such as melanoma, advanced breast cancer, ovarian cancer and pancreatic cancer. The efficacy of these new immunotherapy agents can in theory be enhanced substantially by therapies that stimulate new immunologic (T-cell) responses against the tumor. Laser immunotherapy (LIT) with imiquimod and InCVAX are techniques that produce useful responses in patients with advanced melanoma, the prototypical chemotherapy resistant solid tumor. The mechanism of action of these therapies is thought to be immunological, including the development of new T-cell responses. We have therefore been combining LIT using imiquimod and InCVAX treatment with the new T-cell stimulators (ipilimumab) in cases of stage IV melanoma. While still anecdotal, the use of novel combinations of immunologic therapies should provide much improved responses for chemotherapy-resistant solid tumors (such as melanoma) than was previously possible. Newer T-cell stimulating drugs such as the anti-PD-1 antibodies and anti-PD-L1 antibodies will make this general approach to treating chemoresistant advanced tumors even more effective in the future.

[1]  Q. Myrvik,et al.  Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-D-glucosamine, in mice , 1997, Infection and immunity.

[2]  Michael R Hamblin,et al.  Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model , 2008, Proceedings of the National Academy of Sciences.

[3]  Hailing Lu,et al.  Immunoediting of Cancers May Lead to Epithelial to Mesenchymal Transition1 , 2006, The Journal of Immunology.

[4]  Y. Belkaid Role of Foxp3‐positive regulatory T cells during infection , 2008, European journal of immunology.

[5]  J. Schlom,et al.  Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination. , 2007, Vaccine.

[6]  P. Krammer,et al.  Molecular Mechanisms of Treg-Mediated T Cell Suppression , 2012, Front. Immun..

[7]  Y. Belkaid Regulatory T cells and infection: a dangerous necessity , 2007, Nature Reviews Immunology.

[8]  A. Neunkirchner,et al.  Naturally occurring regulatory T cells: markers, mechanisms, and manipulation , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  Wei R. Chen,et al.  Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine , 2013, Clinical & developmental immunology.

[10]  J. Elias,et al.  Chitin regulation of immune responses: an old molecule with new roles. , 2008, Current opinion in immunology.

[11]  M. Manjili,et al.  Tumor immunoediting and immunosculpting pathways to cancer progression. , 2007, Seminars in cancer biology.

[12]  Robert E. Nordquist,et al.  Clinical effects of in situ photoimmunotherapy on late-stage melanoma patients , 2010, Cancer biology & therapy.

[13]  Hong Liu,et al.  Preliminary safety and efficacy results of laser immunotherapy for the treatment of metastatic breast cancer patients , 2011, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[14]  Hong Liu,et al.  Enhancement of Laser Cancer Treatment by a Chitosan-derived Immunoadjuvant¶ , 2005, Photochemistry and photobiology.

[15]  E. Tagliabue,et al.  FOXP3 expression in tumor cells and implications for cancer progression , 2013, Journal of cellular physiology.

[16]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Erica G. Schmitt,et al.  Generation and Function of Induced Regulatory T Cells , 2013, Front. Immunol..

[18]  R. Nordquist,et al.  In situ photoimmunotherapy: a tumour‐directed treatment for melanoma , 2006, The British journal of dermatology.

[19]  R. Nordquist,et al.  Laser-photosensitizer assisted immunotherapy: a novel modality for cancer treatment. , 1997, Cancer letters.

[20]  Hong Liu,et al.  Effect of different components of laser immunotherapy in treatment of metastatic tumors in rats. , 2002, Cancer research.