TY - JOUR

T1 - Adoptive cell therapy in combination with checkpoint inhibitors in ovarian cancer

AU - Kverneland, Anders Handrup

AU - Pedersen, Magnus

AU - Wulff Westergaard, Marie Christine

AU - Nielsen, Morten

AU - Borch, Troels Holz

AU - Olsen, Lars Rønn

AU - Aasbjerg, Gitte

AU - Santegoets, Saskia J.

AU - van der Burg, Sjoerd H.

AU - Milne, Katy

AU - Nelson, Brad H.

AU - Met, Özcan

AU - Donia, Marco

AU - Svane, Inge Marie

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Adoptive cell therapy

KW - Checkpoint inihibors

KW - Combinational immune therapy

KW - Ovarian cancer

KW - Tumor-infiltrating lymphocytes

U2 - 10.18632/oncotarget.27604

DO - 10.18632/oncotarget.27604

M3 - Journal article

C2 - 32547707

AN - SCOPUS:85090274230

VL - 11

SP - 2092

EP - 2105

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 22

ER -