ASGCT 2020: Novel strategy for generating “off-the-shelf” CAR T-cells that protects against allorejection

Researchers have developed a novel approach to generate an “off-the-shelf” CAR T cell, for the treatment of hematologic malignancies, that avoids allorejection and graft versus host disease.

New research presented at the American Society of Gene & Cell Therapy (ASGCT) 2020 Annual Meeting (12-15 May, 2020) has demonstrated a novel approach to generate an “off-the-shelf” CAR-T cell, for treatment of hematologic malignancies, which avoids allorejection.

There is an urgent need for immediately available CAR-T cells for treatment of hematologic malignancies. However, the potential for polyclonally activated CAR-T cells (ATCs) from unrelated donors to cause graft-versus-host disease, and rejection of allogenic CAR-T cells in patients, has impeded the development of “off-the-shelf” therapies.

Rayne Rouce, Texas Children’s Hospital (TX, USA), and research team, isolated peripheral blood mononuclear cells (PBMCs) from healthy donors to generate CD30+CD19.CAR-Epstein—Barr virus-specific T-cells (dual CAR-EBVSTs). The team examined the phenotype, proliferative capacity and antitumor function of the dual CAR-EBVSTs compared to single CAR-transduced EBVSTs or ATCs. They equipped EBVSTs with a CD30.CAR to examine whether this could eliminate alloreactive T-cells upon exposure to HLA-mismatched PBMCs (containing alloreactive T-cells) in a mixed lymphocyte reaction.

It was found that dual CAR-EBVSTs could be successfully manufactured from multiple healthy donors. The study results also demonstrated that dual CAR-EBVSTs were able to kill CD19 and CD30+ tumor cells in vitro. In addition, dual CAR-EBVSTs were shown to eliminate and, therefore, avoid rejection by HLA-A2+ alloreactive T cells.

Overall, the study outlines a novel approach to generating an “off -the-shelf” CAR-T cell using EBVSTs transduced with both CD19 and CD30 with the ability to avoid rejection.

Source: Hsieh E, Quach D, Dominguez L, Rooney C, Rouce R. An Off-The-Shelf CAR T-Cell Strategy for Hematologic Malignancies That Protects Against GVHD and Allorejection. ASGCT 2020 Annual Meeting (12-15 May 2020). Abstract: 1157.