Chimeric Antigen Receptor (CAR) T Cells

CAR T cell therapy 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 cell 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 cell approach.8,9 Various CAR T cell therapies are currently being investigated for the treatment of hematologic malignancies and solid tumors.

Celgene is developing CAR T cell therapies, including a collaboration with 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. PMID: 24311149
  2. Davilla ML, et al. Oncoimmunology. 2012;1:1577-1583. PMID: 23264903
  3. Mato A, Porter DL. Blood. 2015;126:478-485. PMID: 26065655
  4. Milone MC, et al. Mol Ther. 2009 ;17 :1453-1464. PMID: 19384291
  5. Savoldo B, et al. J Clin Invest. 2011;121:1822-1826. PMID: 21540550
  6. Heiblig M, et al. World J Stem Cells. 2015;7:1022-1038. PMID: 26328018
  7. Tumaini B, et al. Cytotherapy. 2013;15:1406-1415. PMID: 23992830
  8. Kowolik CM, et al. Cancer Res. 2006;66:995-1004. PMID: 17108138
  9. Brentjens RJ, et al. Clin Cancer Res. 2007;13:5426-5435. PMID: 17855649
  10. Seckinger A, et al. Cancer Cell. 2017;31:396-410. PMID: 28262554
  11. Tai Y-T, et al. Immunotherapy. 2015;7:1187-1199. PMID: 26370838
  12. Carpenter RO, et al. Clin Cancer Res. 2013;19:2048-2060. PMID: 23344265
  13. Makita S, et al. Cancer Sci. 2017;108:1109-1118. PMID: 28301076