bb2121 (Anti-BCMA CAR-T)

Proposed Mechanism of Action

bb2121 is an investigational chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells.1,2 The bb2121 CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, CD3-zeta T-cell activation domain proposed to increase T-cell activation, and a 4-1BB domain hypothesized to increase T-cell activation, proliferation, and persistence.1,3-5 bb2121 CAR-T cells are proposed to recognize and bind BCMA on the surface of multiple myeloma cells leading to apoptosis.6,7

bb2121 Proposed Mechanism of Action

bb2121, an investigational CAR-T therapy, is proposed to target BCMA on myeloma cells.

bb2121 by Disease State

bb2121 in Multiple Myeloma

  • Phase 1 Multiple Myeloma

Rationale for Clinical Development

In vitro experiments have shown that bb2121 has displayed activity against BCMA-expressing multiple myeloma, Burkitt lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and plasmacytoma cell lines.8 Preclinical studies have demonstrated that anti-BCMA CAR-T cells secrete cytokines following engagement of BCMA-expressing target cells.9

The safety and efficacy of agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

An investigational anti-BCMA (B-cell maturation antigen) CAR-T cell therapy that is being developed for the treatment of multiple myeloma by Celgene in collaboration with bluebird bio.

References

  1. Berdeja JG, et al. J Clin Oncol. 2017;35(15 suppl):3010-3010.
  2. Seckinger A, et al. Cancer Cell. 2017;31:396-410.
  3. Davila ML, et al. Int J Hematol. 2014; 99:361-371.
  4. Bridgeman, JS, et al. Clin Exp Immunol. 2014;175:258-267.
  5. Dotti G, et al. Immunol Rev. 2014;257:107-126.
  6. Carpenter RO, et al. Clin Cancer Res. 2013;19:2048-2060.
  7. Turtle C. Int J Hematol. 2014;99:132-140.
  8. Chekmasova A, et al. Blood. 2015;126:3094.
  9. Lilley G, et al. Blood. 2015;126:3243.