First Dose of CD38-Targeting CAR T-Cell Therapy Administered in AML

Acute myeloid leukemia (AML) cells in blood flow: © LASZLO - stock.adobe.com

The first dose of KJ-C2320, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD38, has been administered to a patient with relapsed/refractory acute myeloid leukemia (R/R AML) in an investigator-initiated trial.¹

The investigator-initiated trial of KJ-C2320 in R/R AML is ongoing in China.

KJ-C2320 is being developed based on the THANK (Target to Hinder the Attack of NK cells)-uCAR platform through CARsgen Therapeutics.¹ The proprietary platform is designed to enhance the expansion and persistence of allogeneic CAR T cells and leverages modifications in donor-derived T cells.

According to the press release, a challenge often seen with using allogeneic T cells is minimizing graft-vs-host disease (GVHD) and host-vs-graft response (HvGR). To address this, THANK-uCAR technology disrupts the genomic loci encoding T-cell receptors (TCR) and beta-2 microglobulin, which eliminates the surface expression of TCR and human leukocyte antigen class I (HLA-I). This approach has been validated by previous research.

Additionally, when allogeneic T cells lack HLA-I expression, this makes them vulnerable to attacks by natural killer (NK) cells. Attacks by NK cells can limit the expansion and persistence of CAR T cells in the patient. To protect against this, the THANK-uCAR platform arms the modified TCR-/B2M-T cells with a CAR targeting NKG2A. This strategy protects the CAR-T cells from NK cell-mediated rejection, bettering their ability to persist and function effectively.

Clinical studies of BCMA-targeting CAR T-cell therapy developed using the THANK-uCAR platform have already shown encouraging results, demonstrating expansion levels in patients achieving a complete response that were comparable with autologous CAR T cells. Further, the therapy exhibited a controllable safety profile and promising efficacy.

Additional differentiated allogeneic CAR T-cell products are also advancing based on the THANK-uCAR platform, including CT0590, for the treatment of R/R multiple myeloma and plasma cell leukemia, KJ-C2219, which targets CD19 and CD20, for the treatment of B-cell-related hematologic malignancies and autoimmune diseases, and KJ-C2114 for the treatment of patients with solid tumors.²

REFERENCES

1. CARsgen's allogeneic CD38 CAR-T therapy administers first dose in an investigator-initiated trial. News release. CARsgen Therapeutics Holdings Limited. January 20, 2025. Accessed January 20, 2025. https://tinyurl.com/3tkesjrp

2. CARsgen® announces 2024 interim results. News release. CARsgen Therapeutics Holdings Limited. August 29, 2024. Accessed January 20, 2025. https://tinyurl.com/bdz53h8b