Reprogramming T-cells for adoptive immunotherapy of ovarian cancer

ABSTRACT

Introduction: Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients’ outcome, persistent and recurrent EOC remains an un-eradicable disease.

Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs).

CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs.

Areas covered: In this review, we will focus on preclinical and clinical studies evaluating CART activity in EOC in order to identify possible difficulties and advantages of their use in this particular setting.

Expert Opinion: The pattern of diffusion within the peritoneal cavity, the tumor microenvironment and the high rate of TAAs make EOC a particularly interesting model for CART cells use. Data from preclinical studies indicate a potential activity of CARTs in EOC, but robust clinical data are still awaited. Further studies are needed to determine the best methods of administration and the most effective CAR type to treat EOC patients.

KEYWORDS:

• Chimeric antigen receptor
• immunotherapy
• ovarian cancer
• T cell

Article highlights

• Despite the improvements in surgical tecniques and the introduction of new drugs such as PARP inhibitors and antiangiogenetic molecules advanced ovarian cancer is still a not eradicable disease.

• In recent years, immunotherapy has proven to be very effective in treating several types of tumors; a particular type of immunotherapy is represented by CART cells, engineered T lymphocytes expressing a chimeric receptor composed primarily of an extracellular domain, represented by a scFV chain capable of recognizing specific antigens and and of an intracellular domain called TCR zeta which determines the transmission of signals activating the immune response.

• CART cells have demonstred to be effective in the treatment of different hematologic neoplasms while data supporting their potential efficacy in the treatment of solid tumors are poor; furthermore these therapies are associated with potentially severe toxicity and high production costs

• Ovarian cancer appears to be a potential candidate for this type of therapy due to the high number of TAAs, the particular micro-environment that characterizes it, and its tendency to remain confined within the peritoneum even in the advanced stage

• Preclinical evidence seems to indicate a possible activity of CART cells in the treatment of ovarian cancer but data from clinical trials are still scarce, several studies are ongoing and we hope that their results could clarify what is the best type of CART cell to use in ovarian cancer and which patients can benefit from it.

Declaration of interest

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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded