Immunotherapy for ovarian cancer: what's next?

Abstract

In the past decade, we have witnessed important gains in the treatment of ovarian cancer; however, additional advances are required to reduce mortality. With compelling evidence that ovarian cancers are immunogenic tumors, immunotherapy should be further pursued and optimized. The dramatic advances in laboratory and clinical procedures in cellular immunotherapy, along with the development of powerful immunomodulatory antibodies, create new opportunities in ovarian cancer therapeutics. Herein, we review current progress and future prospects in vaccine and adoptive T-cell therapy development as well as immunomodulatory therapy tools available for immediate clinical testing.

Fig 1.

Adoptive transfer of T cells is a powerful approach for the treatment of patients with advanced malignancies. It can be accomplished by the adoptive transfer of previously isolated and expanded tumor-specific tumor-infiltrating lymphocytes (TILs) or the adoptive transfer of ex vivo CD3/CD28-costimulated, vaccine-primed T cells (after high-dose outpatient cyclophosphamide and fludarabine) to rapidly achieve expansion and activation of tumor-specific T cells postvaccine. Alternatively adoptive T-cell transfer using genetically modified T cells, which express exogenous tumor antigen-specific T-cell receptors (TCRs), to mediate objective cancer regression. TAL, tumor-associated lymphocytes; CIR, chimeric immune receptor.

Fig 2.

Improved therapeutic efficacy of vaccines or adoptively transferred T cells can be achieved by modulating immune check points, including activation of effector cells by blocking CTLA4 or PD-1; depletion of regulatory T cells by use of low-dose oral or intravenous cyclophosphamide or through targeting the interleukin-2 (IL-2) receptor α chain, also known as CD25; or activation of professional antigen presenting cells (APCs) by stimulation with CD40 ligands.