Leveraging Epigenetics to Enhance the Efficacy of Cancer-Testis Antigen: A Potential Candidate for Immunotherapy

Abstract

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.

Plain language summary

Despite substantial advancements in prognosis and diagnostic approaches, epithelial ovarian cancer is still the most lethal gynecological malignancy worldwide. In addition to radiotherapy, chemotherapy, hormonal therapy, and surgery, immunotherapy in the clinical setting is promising. Tumor-restricted expression and strong immunogenic potential make cancer-testis/germline antigen (CTA) a potential candidate for efficient T-cell and dendritic cell-mediated cancer immunotherapy. The expression of CTAs is shown to be modulated by a specific epigenetic fine-tuning mechanism. However, the expression and role of CTA in epithelial ovarian cancer immunotherapy are poorly understood. Therefore, in the current work, the authors thoroughly highlight and explore the possible epigenetic mechanisms associated with CTA expression and their implication in T-cell and dendritic cell-based immunotherapy approaches to ovarian cancer. Understanding such a paradigm is essential to adopting a precision medicine approach for better therapeutic options.

Keywords::

• cancer-testis antigen
• CAR-T cell
• dendritic cell
• DNA methylation
• epigenetic
• immunotherapy
• ovary cancer
• T cell
• TIL

Author contributions

R Gupta and BP Jit: equally contributed as first authors, searched the literature, wrote the manuscript and contributed to figures and references; S Kumar, S Mittan, P Tanwer, S Mathur, V Perumal, L Kumar and GK Rath: editing and refining the manuscript; A Sharma: formulated and developed the idea, writing the manuscript.

Acknowledgments

The authors thank Adam R Karpf, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, USA, for his constructive scientific input.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.