Abstract
Immune therapy is a promising field within oncology but has been unsuccessful in ovarian cancer (OC). Still, there is rationale and evidence supporting immune therapy in OC. We investigated the potential for adoptive cell therapy (ACT) from in vitro expanded tumor-infiltrating lymphocytes (TILs) in combination with checkpoint inhibitors (ICI) and conducted immunological testing of ex vivo expanded TILs (REP-TILs).Six patients with late-stage metastatic high-grade serous OC 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.One patient achieved a partial response and 5 others experienced disease stabilization for up to 12 months. Analysis of the REP-TILs with flow- and mass-cytometry show primarily activated and differentiated effector memory T cells. REP-TILs showed in vitro reactivity and expression of inhibitory receptors, such as LAG-3 and PD-1. Furthermore, our data indicate that addition of ipilimumab therapy improves the T cell fold expansion during production, increase the level of CD8 T cell tumor reactivity, and favorably affect the T cell phenotype.We show that the combination of ICI and ACT is feasible and safe. With one partial response and one long-lasting SD, we demonstrated the potential of ACT in OC.
Highlights
Ovarian cancers are frequently infiltrated with immune cells
We investigated the potential for adoptive cell therapy (ACT) from in vitro expanded tumor-infiltrating lymphocytes (TILs) in combination with checkpoint inhibitors (ICI) and conducted immunological testing of ex vivo expanded TILs (REP-TILs)
[4, 5], a feature generally considered as an indication of low immunogenicity and responsiveness to immune therapy [6], we and others have demonstrated tumor reactivity amongst TILs [7] and peripheral blood lymphocytes [8] in ovarian cancer patients suggesting a potential for immune therapy
Summary
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 [1,2,3]. A study in 20 ovarian cancer patients showed an overall response rate (ORR) of 15% with the anti-PD-1 antibody nivolumab [9], but in a recently published, and much larger trial of 294 patients, the ORR was only 8% with the anti-PD-1 antibody pembrolizumab [10]. This is low when compared with the response rates of up to 37% in melanoma and 19% in NSCLC [11,12,13]. The anti-CTLA4 antibody ipilimumab has been tested in ovarian cancer patients, claiming an ORR of 10.3% in a still unpublished trial (NCT01611558)
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