TY - JOUR
T1 - Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer
T2 - a pilot study
AU - Pedersen, Magnus
AU - Westergaard, Marie Christine Wulff
AU - Milne, Katy
AU - Nielsen, Morten
AU - Borch, Troels Holz
AU - Poulsen, Lars Grønlund
AU - Hendel, Helle Westergren
AU - Kennedy, Mia
AU - Briggs, Gillian
AU - Ledoux, Stacey
AU - Nøttrup, Trine Jakobi
AU - Andersen, Pernille
AU - Hasselager, Thomas
AU - Met, Özcan
AU - Nelson, Brad H
AU - Donia, Marco
AU - Svane, Inge Marie
PY - 2018/12/2
Y1 - 2018/12/2
N2 - Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in other cancers. In this pilot study, we tested TIL based ACT in patients with metastatic OC. Methods:Six patients with progressive platinum-resistant metastatic OC were treated with an infusion of TIL preceded by standard lymphodepleting chemotherapy and followed by decrescendo intravenous interleukin-2 (IL-2). Primarily, the feasibility and tolerability of the treatment was assessed. Secondarily, disease control rate was described and immune responses against tumor cells were monitored. Results:Treatment was well tolerated with manageable toxicities. Four patients had stable disease for three months and two patients for five months with five patients having a decrease in target lesions. Progression was primarily due to new lesions while target lesions in general remained stable or in regression. Antitumor reactivity was observed in TIL infusion products from five patients but no antitumor reactivity was detectable in peripheral blood lymphocytes collected after treatment. High numbers of infused TIL expressed exhaustion markers including LAG3 and PD-1, and immunostaining of tumor tissue demonstrated substantial MHCII and PD-L1 expression. Conclusions:ACT with TIL in combination with decrescendo IL-2 is feasible in patients with metastatic OC. Early indications of clinical activity were found. However, TIL ACT efficacy was incomplete with possible involvement of the inhibitory immune checkpoint pathways LAG3/MHCII and PD1/PD-L1.
AB - Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in other cancers. In this pilot study, we tested TIL based ACT in patients with metastatic OC. Methods:Six patients with progressive platinum-resistant metastatic OC were treated with an infusion of TIL preceded by standard lymphodepleting chemotherapy and followed by decrescendo intravenous interleukin-2 (IL-2). Primarily, the feasibility and tolerability of the treatment was assessed. Secondarily, disease control rate was described and immune responses against tumor cells were monitored. Results:Treatment was well tolerated with manageable toxicities. Four patients had stable disease for three months and two patients for five months with five patients having a decrease in target lesions. Progression was primarily due to new lesions while target lesions in general remained stable or in regression. Antitumor reactivity was observed in TIL infusion products from five patients but no antitumor reactivity was detectable in peripheral blood lymphocytes collected after treatment. High numbers of infused TIL expressed exhaustion markers including LAG3 and PD-1, and immunostaining of tumor tissue demonstrated substantial MHCII and PD-L1 expression. Conclusions:ACT with TIL in combination with decrescendo IL-2 is feasible in patients with metastatic OC. Early indications of clinical activity were found. However, TIL ACT efficacy was incomplete with possible involvement of the inhibitory immune checkpoint pathways LAG3/MHCII and PD1/PD-L1.
U2 - 10.1080/2162402x.2018.1502905
DO - 10.1080/2162402x.2018.1502905
M3 - Journal article
C2 - 30524900
SN - 2162-4011
VL - 7
JO - OncoImmunology
JF - OncoImmunology
IS - 12
M1 - e1502905
ER -
