2017 was a watershed year, with the recent approval of chimeric antigen receptor (CAR)-T cell therapy for acute leukemia (tisagenlecleucel) and lymphoma (axicabtagene ciloleucel), as well as a number of new indications for already-approved immune checkpoint inhibitors.

Many expect that genetically engineered T cells and other immune cells combined with other forms of immunotherapy will revolutionize the treatment of cancer in ways unimaginable to scientists and clinicians only a few decades ago.

Yet in unleashing the immune system to destroy cancer, we often endanger normal cells sharing antigens with cancers and other bystanders in the tumor microenvironment; we are therefore faced with the consequences of this process — autoimmune diseases — which can affect various sites including the skin, lungs, intestines, liver, endocrine glands, and nervous system. The need to control or prevent these immune-related adverse events adds to the complexity and potential toxicity of treatment.


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More than 300 CAR-T studies are listed on ClinicalTrials.gov for tumor types ranging from acute leukemia and lymphoma to gastric, hepatic, pancreatic, lung, cervical, ovarian, colorectal, and brain cancers. But patients are typically hospitalized during therapy because of concerns about cytokine release syndrome.

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Another approach with great potential is immunotherapy specific to cancer/testis antigens, which have a highly restricted distribution. Antigens such as NY-ESO-1, with its broad expression in various cancers, is being studied in clinical trials.10,11 In the next decade or 2, I would expect that “off-the-shelf” immunotherapy regimens, including combined cellular therapy, monoclonal antibodies, cytokines, and other targeted therapies will be used to treat cancers with specific genetic mutations safely and effectively.

The future is bright for immunotherapy. As we learn to target the immune response to “self and non-self,” a delicate therapy balance will eventually be achieved with predictable outcomes, benefits, and toxicity in the fight against cancer.

References

  1. Coley WB. The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelas and the bacillus prodigiosus). Proc R Soc Med. 1910;3(Surg Sect):1-48.
  2. Burnet M. Cancer; a biological approach. I. The processes of control. Br Med J. 1957;1(5022):779-86.
  3. Thomas L. On immunosurveillance in human cancer. Yale J Biol Med. 1982;55(3-4):329-33.
  4. Tran E, Robbins PF, Rosenberg SA. ‘Final common pathway’ of human cancer immunotherapy: targeting random somatic mutations. Nat Immunol. 2017;18(3):255-62. doi: 10.1038/ni.368
  5. June CH, Riddell SR, Schumacher TN. Adoptive cellular therapy: a race to the finish line. Sci Transl Med. 2015;7(280):280ps7. doi: 10.1126/scitranslmed.aaa3643
  6. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205-14. doi: 10.1016/j.cell.2015.03.030
  7. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70. doi: 10.1126/science.1203486
  8. Cancer progress timeline. American Society of Clinical Oncology website. https://www.asco.org/research-progress/cancer-progress-timeline. Accessed January 2018.
  9. Hematology/oncology (cancer) approvals & safety notifications. US Food and Drug Administration website. http://wayback.archive-it.org/7993/20170111064250/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm. Updated December 19, 2016. Accessed January 2018.
  10. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22-32.
  11. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914-21. doi: 10.1038/nm.3910