TY - JOUR T1 - IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-002232 VL - 9 IS - 5 SP - e002232 AU - Karan Kohli AU - Lu Yao AU - Theodore Scott Nowicki AU - Shihong Zhang AU - Ralph Graeme Black AU - Brett A Schroeder AU - Erik A Farrar AU - Jianhong Cao AU - Heather Sloan AU - Dawn Stief AU - Lee D Cranmer AU - Michael J Wagner AU - Douglas S Hawkins AU - Venu G Pillarisetty AU - Antoni Ribas AU - Jean Campbell AU - Robert H Pierce AU - Edward Y Kim AU - Robin L Jones AU - Stanley R Riddell AU - Cassian Yee AU - Seth M Pollack Y1 - 2021/05/01 UR - http://jitc.bmj.com/content/9/5/e002232.abstract N2 - Background Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1–specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.Method We performed a phase I clinical trial evaluating the safety of NY-ESO-1–specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.Results Four patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1–specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor–based products at other centers.Conclusions ETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1–specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.Data may be obtained from a third party and are not publicly available. contact Seth.pollack@northwestern.edu for additional information. ER -