T-Cell Receptor Therapy in the Treatment of Ovarian Cancer: A Mini Review

Abstract

Ovarian cancer, in particularly high-grade serous ovarian cancer (HGSOC) and ovarian carcinosarcoma (OCS), are highly aggressive and deadly female cancers with limited treatment options. These tumors are generally unresponsive to immune check-point inhibitor (ICI) therapy and are referred to as immunologically "cold" tumors. Cell-based therapy, in particular, adoptive T-cell therapy, is an alternative immunotherapy option that has shown great potential, especially chimeric antigen receptor T cell (CAR-T) therapy in the treatment of hematologic malignancies. However, the efficacy of CAR-T therapy in solid tumors has been modest. This review explores the potential of another cell-based therapy, T-cell receptor therapy (TCR-T) as an alternate treatment option for immunological "cold" OC and OCS tumors.

Keywords: T-cell receptor; cell-based therapy; immunotherapy; ovarian cancer; tumor neoantigen.

Figure 1

(A) Ovarian cancer can be classified into four subtypes based on their cell of origin and histological characteristics. Epithelial OC is the most common subtype of OC, which can be further divided into 5 histological groups. HGSOC is the most common subtype of EOC accounting for about 70% of cases and is associated with the poorest prognosis. HGSOC can be further molecularly sub-classified based on its gene expression profile, into 4 groups (C1, C2, C4 and C5). Ovarian or fallopian tube derived carcinosarcoma (O/FTCS) is a rare subtype of OC and may belong within the spectrum of HGSOC tumor. (B) CIRCOS plots of a patient with HGSOC (top) and a patient with OCS (bottom) with low tumor mutation burden – demonstrating a high degree of chromosomal instability (C) Schematic diagram of tumors with high and low tumor mutation burdens versus inflamed and non-inflamed immunophenotypes based on their T-cell and IFN signature. Although some ovarian cancers may have low TMB, these tumors may still respond to ICI if they are associated with a “hot” immunophenotype. Completely “cold” tumors are those associated with low TMB and cold immunophenotype features, such as pancreatic, prostate cancer and some OCS.