1017P - Phenotypic and functional characterization of tumor infiltrating lymphocytes (TIL) grown from non-hodgkin lymphoma tumors: Implications for the development of novel therapies for lymphoma

Abstract

Background: Cell therapy with TIL is an effective treatment with acceptable safety profile for advanced metastatic melanoma patients. TIL products can be centrally manufactured for broad clinical application. Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL, lymphodepletion of the patient prior to infusion of TIL, followed by infusion of TIL and treatment with IL-2. Here, we present findings related to expanding TIL directly from lymphoma. Methods: Using methods for TIL isolation and growth developed at Lion, we expanded TIL from 5/5 lymphoma (1 MCL, 3 follicular, 1 DLBCL) with Interleukin 2 for 11-14 days and subsequent rapid expansion for 14 days using mitogenic anti-CD3 antibody and irradiated allogeneic PBMC. Results: TIL were generated from all 5 lymphoma tumors with a maximum expansion index of 680-fold, significantly higher than previously reported. Mean CD3+ T cell population was 95% (vs 75% previously reported). As with TIL expansion from melanoma, we observed a marked relative increase in effector memory cells in lymphoma TIL. A significant increase in TEMRA (p = 0.0013; CD4, CD8) and CD28+CD4 + (p = 0.008) subsets was observed in lymphoma compared with melanoma TIL cultures. Bioluminescent Redirected Lysis Assay (BRLA) to assess TIL cytolytic activity at 4 hrs ranged from <1-6 LU50 in lymphoma TIL compared to melanoma TIL (11-75 LU50, 4hrs). ELISpot and ELISA analysis revealed IFN-γ production by lymphoma TIL comparable to that of melanoma TIL. Consistent with the observation that lymphoma-reactive T-cells are primarily TH2 and TH17, nanostring analysis revealed that lymphoma TIL expressed higher levels of RORC and IL17A than melanoma TIL. Conclusions: We demonstrate here the feasibility of growing TIL from lymphoma that have effector functions comparable to that of melanoma TIL. These findings serve as a rationale for considering TIL cell therapy for patients with lymphoma. Legal entity responsible for the study: Lion Biotechnologies, Inc Funding: Lion Biotechnologies Inc Disclosure: L. Karyampudi, A. Gokuldass, M. Blaskovich, M.T. Lotze: Employee of Lion Biotechnologies, Inc, receive compensation from Lion. Hold stock and/or stock options in Lion Biotechnologies, Inc. M. Fardis: Employee and director of Lion Biotechnologies, Inc, receive compensation from Lion. Hold stock and/or stock options in Lion Biotechnologies, Inc. Member of the Board of Directors of Lion Biotechnologies, Inc.