Abstract 1423: AIM ACT, a novel nanoparticle-based technology that generates therapeutic numbers of functional tumor-specific CD8+ T cells with T stem cell, central and effector memory phenotype in 14 days
Authors: Kim Sojung , Suarez Lauren , Lu Emily , Walmacq Celine , Dembrow Daniel , Varela Juan , Bednárik Dan , Carter Kenneth , Pandya Naimish , Jones Kristi , Oelke Mathias 
Published: August 2019

Background:

Efficient ex-vivo generation of functional tumor-specific T cells with an optimal memory phenotype remains a significant hurdle to the broad application of adoptive cell transfer (ACT) protocols for the treatment of cancer. Genetically engineered T cells represent a currently available option, but the genetic manipulation of T cells presents significant challenges in terms of manufacturing, cost and addressing tumor escape mechanisms. Here, we describe a novel nanoparticle-based approach for generating tumor-specific T cells at clinical grade and scale from the endogenous T cell repertoire using artificial antigen presenting cells (aAPC).

Methods:

aAPC consist of a paramagnetic nanoparticle to which humanized HLA-A2-Ig dimer-molecules and anti-CD28 antibodies are covalently linked. aAPC are loaded with multiple HLA-A2 restricted peptides and used to magnetically enrich and expand tumor-specific CD8+ T cells. Using peptide loaded aAPC, a fully enclosed and automated GMP T cell expansion platform has been developed that consistently generates clinically relevant numbers of tumor-specific, T stem cell, central and effector memory CD8+ T cells in 14 days, providing an alternative to genetically manipulated T cells.

Results:

Starting from a healthy donor leukopak, tumor-specific CD8+ T cells were generated using an aAPC cocktail loaded with 5 HLA-A2 epitopes from AML tumor antigens WT1, PRAME and Cyclin A1. On average, 1-2 x109 T cells were generated that were &gt;90% of the memory phenotype that averaged 18% T stem cells, 40% central memory and 35% effector memory CD8+ T cells. AML-specific T cells were expanded 500 to &gt;5000-fold from low frequency precursor populations. The system has also been used to generate MM specific T cells of the same quality from both from fresh leukopacks and cryopreserved PBL. All generated T cells were fully functional, as demonstrated by intra-cellular cytokine analysis and tumor cell killing.

Conclusion:

AIM ACT is a novel nanoparticle-based T cell platform developed for the rapid, streamlined generation of clinically-relevant numbers of tumor-specific, T stem cell, central and effector memory CD8+ T cells from donor PBMC in 14 days. The platform described here will be used to generate multi-antigen specific CD8+ T cell products that will be evaluated in multi-center P1/2 clinical trials. These trials will enroll r/r MM patients and r/r AML patients pre- and post-allogeneic hematopoietic stem cell transplant. The flexibility of the AIM ACT system, as shown has potential for clinical evaluation in other hematological tumors and can be used for targeting neo-epitopes.

Citation Format: Sojung Kim, Lauren Suarez, Emily Lu, Celine Walmacq, Daniel Dembrow, Juan Varela, Dan Bednárik, Kenneth Carter, Naimish Pandya, Kristi Jones, Mathias Oelke. AIM ACT, a novel nanoparticle-based technology that generates therapeutic numbers of functional tumor-specific CD8+ T cells with T stem cell, central and effector memory phenotype in 14 days [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1423.