Immunotherapy: A Glimmer of Hope for Metastatic Prostate Cancer

Vishal Jindal

Disclosures

Chin Clin Oncol. 2018;7(6) 

In This Article

Future Directions

Vaccine Immunotherapy in Early Stages of Cancer

Vaccine immunotherapy is not a direct cancer cell lytic therapy, basically it enhances the immune system to fight against cancer cells and which is a slow process and has to go through multiple steps. And as cancer progresses it has suppressive effect on immune system, and with advanced stages of cancer reactivation of immune system will not be an easy task. Clinical data involving several tumor types have shown that vaccine immunotherapy works best in early stages of disease with limited tumor burden.[65,66] It has been shown that there is threefold increase in inflammatory cells in tumor microenvironment when they are treated with Sipuleucel-T prior to radical prostatectomy.[7]

Biomarkers. Failure of individual immune check point inhibitors raised the question whether expression of PD-1/PD-L1/CTLA-4 is biomarker for efficacy of immune checkpoint inhibitors. Immune biomarkers are required to increase the efficacy and to reduce the side effect profile. Further studies need to be conducted to look for more specific biomarkers.

Prostate cancer antigens. Immunotherapy vaccines target the antigens which are present normally on prostate like PAP, PSA, prostate specific cell antigen. Prostate cancer undergoes significant somatic mutations and several mutated proteins can serve as a neoantigens.[67] If we can find and target these new mutated proteins, efficacy and specificity of vaccine will significantly improve.

Novel targets for immune checkpoint. Finding new immune checkpoints which creates tumor resistance will be the key to design new therapies for cancers. Recently it was discovered that ipilimumab therapy in prostate cancer had led to high level of T cell infiltration along with that there is increased expression of PD-L1 and VISTA (V domain Ig suppressor of T Cell activation), another immune checkpoint.[68] Therefore, addition of anti-VISTA therapy to previous immune check point inhibitors can open new frontiers in immunotherapy for prostate cancer. Some other potential targets for immunotherapy of solid tumors are under initial stages of study. Some of them are LAG-3, TIGIT, TIM-3, B7-H3, B7-H4, CD-27, OX40, IDO, CD39, CD73, STAT3, CD137, PSMA, FAP/IL-2.

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