Cell therapies in ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo, and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy.

Short term inhibition of immune checkpoint proteins increases ex vivo expansion of tumour infiltrating lymphocytes in high grade serous ovarian cancer

“…TIL therapy offers an important new therapeutic approach to patients with HGSOC, although, to date, response rates equivalent to those demonstrated in metastatic melanoma using established TIL manufacture techniques have not been achieved in ovarian cancer (Sarivalasis et al, 2021, Pedersen et al, 2018. A contemporary clinical trial of TIL therapy in ovarian cancer has demonstrated limited e cacy compared to metastatic melanoma trials, with all patients achieving a best response of stable disease and a progression free survival between 3-5 months (Pedersen et al, 2018).…”

Integrative bioinformatics and experimental analysis revealed down-regulated CDC42EP3 as a novel prognostic target for ovarian cancer and its roles in immune infiltration

“…It was found that CDC42EP3 had the most relevance with several TILs, including NK cell, Tcm_CD4 and Tgd. NK-based immunotherapy strategy, especially cytokine-induced killer (CIK) cells, has been extensively studied for decades ( Sarivalasis et al, 2021 ). The clinical efficacy of CIK cells was evaluated in patients with advanced epithelial ovarian cancer in a phase 3 clinical trial.…”

Dendritic Cell Vaccines: A Promising Approach in the Fight against Ovarian Cancer

“…While the therapy was safe and only resulted in grade 1 or 2 toxicities, no reduction in tumor burden was observed in any of the six tested patients [ 25 ]. This and several other clinical trials in OC targeting different antigens have demonstrated the poor success of CAR T-cell therapies in OC, much like in several other solid tumors [ 24 , 26 ]. TCR T-cell therapy in OC on the other hand is still in its early phase with 19 Phase I/II clinical trials registered in (accessed on 15 August 2022).…”

“…On the other hand, CAR T-cell therapy uses antigen-binding regions of antibodies that are fused to intracellular T-cell signaling domains, thereby allowing them to recognize surface antigens independent of HLA presentation. However, while CAR T cells can only elicit an immune response to surface antigens, TCR T cells can recognize antigens from any subcellular compartment [ 24 ]. 32 Phase I/II clinical trials of CAR T-cell therapies have been registered in (accessed on 15 August 2022) directed towards several antigens including B7-H3, TAG72, ALPP, CD133, C-met, FRα, FRβ, HER2, mesothelin, and MUC-1.…”