CARsgen Therapeutics is making strides in allogeneic CAR-T cell therapy through its THANK-u Plus platform. Several milestones have been achieved, marking progress in treating hematologic malignancies. These include the administration of the first dose of KJ-C2219, an allogeneic CAR-T therapy targeting CD19/CD20, in an investigator-initiated trial (IIT) for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Additionally, a patient with relapsed/refractory multiple myeloma (R/R MM) achieved a stringent complete response (sCR) and minimal residual disease (MRD) negativity at the Day-28 assessment following treatment with an allogeneic BCMA CAR-T therapy developed on the THANK-u Plus platform. Furthermore, the first dose of KJ-C2320, an allogeneic CAR T-cell therapy targeting CD38, has been administered to a patient with relapsed/refractory acute myeloid leukemia (R/R AML) in an IIT.
Advancing Allogeneic CAR-T Therapy with THANK-u Plus
CARsgen's THANK-u Plus platform is an enhanced version of its proprietary THANK-uCAR® allogeneic CAR-T technology. It is designed to address the potential impact of NKG2A expression levels on therapeutic efficacy. The THANK-u Plus platform demonstrates sustained expansion regardless of varying NKG2A expression levels on NK cells and exhibits significantly improved expansion compared to THANK-uCAR®. Preclinical studies have shown that THANK-u Plus delivers superior antitumor efficacy in the presence of NK cells compared to THANK-uCAR®.
Clinical Trial Updates and Efficacy Data
The first subject treated with an allogeneic BCMA CAR-T therapy developed on the THANK-u Plus™ platform achieved stringent complete response (sCR) and minimal residual disease (MRD) negativity at the Day-28 assessment. The patient, diagnosed with relapsed/refractory multiple myeloma, IgA-λ type (R-ISS Stage II), had previously undergone three lines of combination therapy along with autologous hematopoietic stem cell transplantation. After disease progression following the most recent treatment, the patient was enrolled in the clinical trial. Following infusion of CAR‑T cells at the lowest dose level according to the clinical protocol, the patient experienced Grade 1 cytokine release syndrome (CRS), which was effectively managed with antipyretics and tocilizumab, and the patient did not show immune effector cell-associated neurotoxicity syndrome (ICANS) or other CAR-T-related immune adverse events, demonstrating an overall favorable safety profile.
Overcoming Challenges in Allogeneic CAR-T Therapy
Allogeneic CAR-T cell therapies face challenges such as graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR). CARsgen's THANK-uCAR technology disrupts the genomic loci encoding T-cell receptors (TCR) and beta-2 microglobulin, eliminating the surface expression of TCR and human leukocyte antigen class I (HLA-I). This approach minimizes GvHD and HvGR. To protect the allogeneic CAR-T cells from the patient's NK cells' attacks, CARsgen arms 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.
CARsgen's Pipeline and Future Directions
CARsgen is advancing a pipeline of allogeneic CAR-T cell products based on the THANK-uCAR platform, including CT0590 for R/R multiple myeloma and plasma cell leukemia, KJ-C2219 for B-cell-related hematologic malignancies and autoimmune diseases, and KJ-C2114 for solid tumors. These therapies aim to improve safety, enhance efficacy, and reduce treatment costs, with the goal of making cancer curable.
