Oncotarget: Adoptive cell therapy in combination with checkpoint inhibitors


Volume 11, Issue 22 of @Oncotarget reported that there are rationale and evidence supporting immune therapy in Ovarian Cancers. The authors investigated the potential for adoptive cell therapy from in vitro expanded tumor-infiltrating lymphocytes in combination with checkpoint inhibitors and conducted immunological testing of ex vivo expanded TILs.

Six patients with late-stage metastatic high-grade serous Ovarian Cancer were treated with immune therapy consisting of ipilimumab followed by surgery to obtain TILs and infusion of REP-TILs, low-dose IL-2, and nivolumab.

Analysis of the REP-TILs with the flow- and mass-cytometry show primarily activated and differentiated effector memory T cells.

Furthermore, the authors' data indicate that the addition of ipilimumab therapy improves the T cell fold expansion during production, increases the level of CD8 T cell tumor reactivity, and favorably affects the T cell phenotype.

Dr. Inge Marie Svane from The National Center for Cancer Immune Therapy, Department of Oncology at Copenhagen University Hospital in Denmark said, "Ovarian cancers are frequently infiltrated with immune cells. T cell infiltration and, especially the number of CD8 T cells, is correlated to longer survival in ovarian cancer patients."

"T cell infiltration and, especially the number of CD8 T cells, is correlated to longer survival in ovarian cancer patients"

While ovarian cancer is characterized by a low to an intermediate mutational burden, a feature generally considered as an indication of low immunogenicity and responsiveness to immune therapy, the authors and others have demonstrated tumor reactivity amongst TILs and peripheral blood lymphocytes in ovarian cancer patients suggesting a potential for immune therapy.

Several clinical trials have tested ICI in ovarian cancer patients but so far with very modest results.

A study in 20 ovarian cancer patients showed an overall response rate of 15% with the anti-PD-1 antibody nivolumab, but in a recently published, and much larger trial of 294 patients, the ORR was only 8% with the anti-PD-1 antibody pembrolizumab.

Figure 6: Therapy regimen.

Figure 6: Therapy regimen. Overview and timeline of the trial with conditioning chemotherapy, adoptive cell therapy and checkpoint inhibitors during the clinical trial.

The same authors here, recently published results from a small ACT pilot trial in ovarian cancer demonstrating feasibility but with no patients achieving objective responses.

The Marie Svane Research Team concluded in their Oncotarget Research Paper that ACT for ovarian cancer is still in its cradle compared to malignant melanoma that is presently in phase III clinical testing.

However, accumulative evidence points towards a potential role of immunotherapy in ovarian cancer but with a modest efficacy of established ICIs. Thus, combination immunotherapy might be a way forward supporting the continuous development and refinement of ACT therapy for this purpose.

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DOI - https://doi.org/10.18632/oncotarget.27604

Full text - https://www.oncotarget.com/article/27604/text/

Correspondence to - Inge Marie Svane - [email protected]

Keywords - adoptive cell therapy, tumor-infiltrating lymphocytes, ovarian cancer, combinational immune therapy, checkpoint inihibors

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