Rapid Expansion of Tumor-specific T cells using Artificial Antigen Presenting Cells for Adoptive Immunotherapy
Juan Carlos Varela1, Carl Haupt1, Joan Bieler2, Chrystal Paulos1, Mathias Oelke3, Jonathan Schneck2
1Hollings Cancer Center, MUSC, Charleston, SC, USA; 2Dept. of Pathology, Johns Hopkins University, Baltimore, MD, USA. 3NexImmune, Gaithersburg, MD, USA
Efficient ex-vivo generation of antigen-specific T cells remains a significant hurdle for the broad application of adoptive cell transfer (ACT) protocols. We have recently described a novel nanoparticle-based method for the expansion of tumor-specific T cells using artificial antigen presenting cells (aAPCs) termed Enrichment and Expansion (E+E). Using E+E, we were able to rapidly generate large numbers of antigen-specific T cells targeting 1) the tumor antigens MART1 and NY-ESO-1 and 2) predicted neoepitopes.
Average percentages of antigen-specific T cells on day 14 were 70% for MART1 and 39% for NY-ESO-1. Average fold expansion on day 14 for MART1 and NY-ESO-1 specific T cells were >9200-fold for both populations. Analysis of memory phenotype revealed that on day 0 most T cells in the cultures were of the naïve phenotype while on day 14 the majority MART1 and NY-ESO-1-specific T cells were of the central memory phenotype. Analysis of the of the expression of IL-2, IFN-g, TNF-a, MIP-1b, and CD107 by MART1 and NY-ESO-1-specific T cells on day 14 showed that T cell cultures obtained via E+E were highly polyfunctional. In addition, expression of PD-1, CTLA-4, TIM-3 and LAG-3 was not significantly elevated in the antigen-specific T cells. Finally, we were able to expand T cells specific for predicted neoepitopes from the breast cancer cell line MCF7. After detection of tumor-specific mutations and prediction of immunogenic epitopes, we successfully generated highly polyfunctional neoepitope-specific T cells from normal human donors using our aAPCs and our E+E platform.
Here, we report that E+E is a feasible, simple and streamlined approach to rapidly generate large numbers of tumor-specific T cells from rare naïve precursors and predicted neo-epitope responses.