Abstract 1531: Development of PBMC derived tumor effector cells with potent pan-cancer cytolytic activity for autologous cellular immunotherapy

Abstract

Abstract Introduction: A unique autologous cellular therapeutic (SUPLEXA) has been developed from human PBMC. It is comprised of NK cells, γδ T cells and CD8+ T effector cells, capable of broadly lysing a variety of tumor cell lines in vitro. SUPLEXA cells are manufactured using an efficient 2 week xeno-free manufacturing procedure employing two proprietary engineered leukocyte stimulator cell lines (ENLIST) that express an array of immunomodulatory proteins. The SUPLEXA cell manufacturing process is highly reproducible and demonstrates low inter-subject variability in cellular composition. SUPLEXA cells are distinguished from many other cellular approaches in that they are derived from autologous PBMC that have only been stimulated with ENLIST cells through naturally occurring receptors without any genetic modification. Here, we report on the in vitro characterization of SUPLEXA cytolytic activity on a variety of target tumor cell lines. Results: We prepared SUPLEXA cells from the PBMC of a variety of solid tumor patients (5 melanoma and 5 prostate). Yields and cell characterization by mass cytometry (CyTOF) yielded similar profiles within the variability expected for all the major cell subtypes. SUPLEXA cells were comparatively assessed for cytolytic activity on 4 tumor cell lines; K562 (leukemia), PC3 (prostate), M14 (melanoma) and COLO205 (colorectal cancer). In all instances, cytotoxicity was observed in a quantitative flow cytometry and microscopic assay and was titratable with cell number. Dose-dependent cytolysis was observed for all tumor lines, even at low E:T ratios of 1:10 suggesting that SUPLEXA cells acquire efficient and broad tumor cell lysis activity. Supernatants from cytolysis assays were analyzed for cytokine levels by a 35-plex assay revealing a remarkably restricted cytokine profile with constitutively high levels of RANTES production by the SUPLEXA cells and titratable levels of induced IL-6, IFN-γ and IL-8 production. Conclusions: SUPLEXA cells represent an easy to manufacture autologous anti-tumor cell therapy that overcomes many of the limitations associated with previous autologous therapies. They possess a broad anti-tumor activity at exceedingly low E:T ratios with specific production of IFN-γ, IL-6 and IL-8 during tumor cell killing. Ongoing efforts are underway to understand the relative contributions of NK cells, γδ T cells and CD8+ T cells to broad tumor cytolysis and the antigen-specificities seen with SUPLEXA cells from multiple donors. Planning for a first in human clinical trial is currently underway. Citation Format: Frank Borriello, Joshua W. Keegan, James A. Lederer. Development of PBMC derived tumor effector cells with potent pan-cancer cytolytic activity for autologous cellular immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1531.