Atara Biotherapeutics presents ‘positive’ preclinical data on ATA3431 at ASH

Atara Biotherapeutics announced preclinical data on ATA3431, a next-generation allogeneic CD20/CD19-dual targeted chimeric antigen receptor EBV T-cell therapy candidate. Findings support ATA3431 advancement into clinical testing, initially focused on the treatment of B-cell malignancies, the company said in a statement. The data will be presented in a poster presentation at the 65th American Society of Hematology Annual Meeting taking place December 9-12, 2023, in San Diego. Compared to an autologous CD20/CD19 CAR-T benchmark, the ATA3431 preclinical data demonstrate potent antitumor activity, long-term persistence, and superior tumor growth inhibition. Data highlights include: In functional evaluation, ATA3431 showed stable CAR expression with a predominantly CD8+ T-cell distribution. The 1XX signaling domain and optimized manufacturing process that enriches for a less differentiated phenotype yielded a high central memory population compared with autologous CD20/CD19 bispecific CAR-T cells, achieving consistent killing of CD20+ and/or CD19+ tumor cells following repeated in vitro challenges. ATA3431 demonstrated minimal alloreactivity against HLA mismatched targets due to the inherent ability of EBV T cells to recognize defined viral antigens. The cells also showed HLA-independent activity against CD20+/CD19+ targets in vitro. ATA3431 mediated highly potent tumor growth inhibition in a lymphoma animal model that correlates with long-term persistence without additional exogenous cytokine support. ATA3431 showed superior in vivo anti-tumor efficacy, survival, and functional persistence, in both CD19 high- and low-expressing lymphoma models, compared to autologous benchmark CAR-T cells with no observed treatment-related toxicities. This demonstrates ATA3431’s potential to overcome antigen escape, which is hypothesized to be a major cause of treatment resistance or disease relapse with current CD19-targeted CAR-T treatment.