The immune system plays an active role in the pathogenesis of
ovarian cancer (OC), as well as in the mechanisms of
disease progression and overall survival (OS).
Immunotherapy in gynecological
cancers could help to revert immunosuppression and lymphocyte depletion due to prior treatments. Current
immunotherapies for
ovarian cancer, like all
cancer immunotherapy, are based on either stimulating the immune system or reverting immune suppression. Several approaches have been used, including therapeutic
vaccines,
monoclonal antibodies; checkpoint inhibitors and adoptive T cell transfer. Most of these
therapies are still in early-phase testing (phase I and II) for
ovarian cancer, but the initial data in
ovarian cancer and successful use in other types of
cancers suggests some of these approaches may ultimately prove useful for
ovarian cancer as well.
Ovarian cancer vaccines have shown only a modest benefit in
ovarian cancer when used as monotherapy, but these agents may be able to enhance antitumor activity when combined with
chemotherapy, checkpoint inhibitors, or other
immunotherapies.
Monoclonal antibodies have been explored in
ovarian cancer but despite encouraging phase II data, randomized studies failed to demonstrate significant clinical benefit. Check point inhibitors have promising activity in several solid
tumors and have demonstrated a favorable toxicity profile. Data from early clinical trials utilizing PD1 and
PD-L1 inhibitors showed encouraging results. Ongoing clinical trials are evaluating the role of check point inhibitors in combination with
chemotherapy. Adoptive T cell transfer involves the infusion of ex vivo activated and expanded
tumor specific T cells, using various sources and types of T cells. While this approach has been explored in several
hematologic malignancies, it constitutes early research in
ovarian cancer.
Immunotherapy remains investigational in
ovarian cancer and the benefit of this approach in improving progression-free survival (PFS) or OS is unknown. Previous clinical trials have not selected patients based on
biomarkers and this may explain the negative results. We expect to discover that
tumor response will relate to the patient's immune features and specific
tumor characteristics. We are only beginning to realize the potential of
immunotherapy for
ovarian cancer patients, and one goal of future clinical trials will be to identify subsets of patient based on histologic, molecular, and immune characteristics.