CARsgen Therapeutics Holdings Limited , a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that KJ-C2320, an allogeneic CAR T-cell therapy targeting CD38, has administered the first dose to a patient in an investigator-initiated trial (IIT).

KJ-C2320 is developed based on CARsgen's THANK-uCAR^® platform. An investigator-initiated trial is ongoing in China to evaluate KJ-C2320 for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).

THANK (Target to Hinder the Attack of NK cells)-uCAR^® is CARsgen's proprietary technology to generate allogeneic CAR-T cells with improved expansion and persistence by modifying donor-derived T cells. To minimize graft versus host disease (GvHD) and host versus graft response (HvGR) from allogeneic T cells, we disrupt the genomic loci encoding TCR and beta-2 microglobulin (B2M) to eliminate surface expression of the TCR or the human leukocyte antigen class I (HLA-I), an approach that has been validated by previous research. However, natural killer (NK) cells can attack T cells without HLA-I expression, which then limits the expansion and persistence of the allogeneic CAR-T cells.

To protect the allogeneic CAR-T cells from the patient's NK cells' attacks, we arm these TCR^-/B2M^-T cells with a CAR that recognizes NKG2A to hinder the NKG2A-positive NK cell rejection of the CAR T cells and therefore allow the THANK-uCAR-T cells to resist the attack by NK cells. Clinical studies have demonstrated that the BCMA CAR-T therapy developed on the THANK-uCAR^® platform can expand in patients achieving complete response to levels comparable to autologous CAR-T, showing preliminary evidence of controllable safety and promising efficacy.