Chimeric Antigen Receptor T Cells (CAR-T)

CAR-T Overview

CAR-T utilizes autologous T cells from a patient that have been modified with a chimeric antigen receptor (CAR).1 CARs are composed of an antigen-recognition domain, which is most often a single-chain variable fragment derived from a monoclonal antibody or an antigen-binding fragment, fused to signaling domains designed to redirect T cell function.1,2 CARs can allow the modified patient T cells to recognize tumor-cell antigens and initiate an immunologic response.1-3 Tumor cells are either targeted directly by CAR-modified T cells or through recruitment of other components of the immune system.1

See below for a depiction of the CAR-T engineering process and description of identified targets (B-cell maturation antigen [BCMA] in multiple myeloma and CD19 in non-Hodgkin lymphoma).

Rationale for Clinical Development

Preclinical studies have demonstrated the activity of the CAR-T approach.8,9 Various CAR-T therapies are currently being investigated for the treatment of hematologic malignancies and solid tumors.

CAR-T therapies are being developed in collaboration with Juno Therapeutics and bluebird bio.

The safety and efficacy of the 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.

References

  1. Davilla ML, et al. Int J Hematol. 2014;99:361-371.
  2. Davilla ML, et al. Oncoimmunology. 2012;1:1577-1583.
  3. Mato A, Porter DL. Blood. 2015;126:478-485.
  4. Milone MC, et al. Mol Ther. 2009 ;17 :1453-1464.
  5. Savoldo B, et al. J Clin Invest. 2011;121:1822-1826.
  6. Heiblig M, et al. World J Stem Cells. 2015;7:1022-1038.
  7. Tumaini B, et al. Cytotherapy. 2013;15:1406-1415.
  8. Kowolik CM, et al. Cancer Res. 2006;66:995-1004.
  9. Brentjens RJ, et al. Clin Cancer Res. 2007;13:5426-5435.
  10. Seckinger A, et al. Cancer Cell. 2017;31:396-410.
  11. Tai Y-T, et al. Immunotherapy. 2015;7:1187-1199.
  12. Carpenter RO, et al. Clin Cancer Res. 2013;19:2048-2060.
  13. Makita S, et al. Cancer Sci. 2017;108:1109-1118.