Harnessing Allogeneic Anti-CD22 CAR-T Cells: A Promising Pre-Clinical Approach for B-Cell Acute Lymphoblastic Leukemia

This abstract discusses the development and testing of a novel immunotherapy using engineered T-cells with chimeric antigen receptors (CARs) targeting CD19 for the treatment of B-cell acute lymphoblastic leukemia (B-ALL). The study addresses the limitations of patient-specific CAR T-cell production by exploring the use of allogeneic "off-the-shelf" CAR T-cells from healthy donors. The research focuses on the CD22 antigen, which is present in both B-ALL and healthy B-cells, as a potential target for CAR T-cells.

The engineered T-cells, termed UCART22, express an anti-CD22 CAR and a safety ligand, RQR8, which allows for the control of T-cell activity with rituximab. To minimize the risk of alloreactivity, the expression of the T-cell receptor (TCR) is eliminated through gene editing. The study measured CD22 expression levels in patient samples and B-ALL cell lines, revealing higher expression in certain cell lines.

In vitro experiments demonstrated that UCART22 cells exhibited significant cytotoxic activity against B-ALL cells, which correlated with the level of CD22 expression. Additionally, cytokine secretion assays showed that UCART22 cells produced high levels of IFNγ, TNFα, IL-5, IL-17A, and IL-17F in response to CD22-positive B-ALL stimulation.

Animal studies involving immune-compromised mice with Daudi cell implants, a CD22-positive Burkitt's lymphoma cell line, showed that UCART22 treatment reduced disease burden and extended survival in a dose-dependent manner. Further studies using patient-derived xenografts are underway and will provide additional evidence for the potential of UCART22 in B-ALL immunotherapy.