Harnessing the Potential of Anti-BCMA CAR-T Therapy: A Breakthrough in the Treatment of Relapsed or Refractory Multiple Myeloma

CBMG has engineered a cutting-edge CAR-T cell therapy called C-CAR088, which is aimed at BCMA, a protein predominantly found on cells affected by multiple myeloma. The therapy is crafted to enhance its effectiveness by increasing its specificity and reducing its potential to provoke an immune response, achieved by combining a high-affinity human monoclonal antibody's scFv with a CD3ζ/4-1BB signaling domain.

In laboratory studies, T cells modified with a lentiviral vector carrying the C-CAR088 gene demonstrated targeted capabilities such as proliferation, cytokine release, and the ability to destroy BCMA-positive cancer cells. Importantly, these cells did not react to soluble BCMA protein or serum from multiple myeloma patients. However, they were effective in eliminating BCMA-positive cancer cells in living organisms, including the RPMI-8226 multiple myeloma tumor model. C-CAR088 is produced in a state-of-the-art, closed system devoid of serum, which automates and digitizes the process, yielding CAR-T cells with a stable and high Tcm phenotype. The therapy has shown significant tumor inhibition and survival benefits in animal studies, with the effects being dose-dependent.

A Phase 1 clinical trial is underway for individuals with relapsed/refractory multiple myeloma (r/r MM) who have undergone at least three prior treatments, including those with PI and IMiD or double-refractory conditions, to evaluate the safety and efficacy of C-CAR088 (NCT03815383). Participants undergo apheresis to collect T cells, which are then transformed into C-CAR088 and administered intravenously following a standard conditioning treatment. As of July 5, 2019, three patients have received C-CAR088 at a dosage of 1.0 x 106 CAR-T cells per kilogram of body weight. Despite having received an average of seven prior treatment lines and failing IMiD and PI therapies, all three patients exhibited clinical improvements within two weeks of treatment. The proliferation and expansion of C-CAR088 in the bloodstream were linked to a reduction in tumor load. Two patients achieved very good partial remission (VGPR) at 4 and 8 weeks post-treatment, respectively, while the third patient achieved partial remission (PR) within just two weeks. The treatment was well-tolerated, with no dose-limiting toxicities and only reversible Grade 1-2 cytokine release syndrome (CRS) observed.

The early clinical trial results for r/r MM patients using C-CAR088 are in line with preclinical data, indicating that the therapy is promising in terms of efficacy and safety. The early clinical efficacy observed at a low, suboptimal dose is particularly encouraging and is on par with other anti-BCMA CAR-T products at similar dosages. Further confirmation of these positive trends is expected through the continuation of the clinical trial.

Disclosures: Multiple individuals are listed as having employment and equity ownership with Cellular Biomedicine Group Inc, including Yao, Zhu, Huang, Wei, Lan, LV, Wu, Wang, Yang, Zheng, Zhao, Zhang, Chen, Li, Ren, and Humphries.