Lisocabtagene Maraleucel (Liso-Cel; JCAR017; Anti-CD19 CAR T Cells)

Proposed Mechanism of Action

Liso-cel is an investigational chimeric antigen receptor (CAR) T cell therapy designed to target CD19,1,2 which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells.3-5 Liso-cel CAR T cells aim to target and kill non-Hodgkin lymphoma cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T-cell proliferation and persistence, and a CD3-zeta T-cell activation domain.1,2,6-9 The defined composition of liso-cel may limit product variability; however, the clinical significance of defined composition is unknown.1,10

Liso-Cel Proposed Mechanism of Action


Liso-cel, an investigational CAR T cell therapy, is proposed to target CD19-expressing cells in non-Hodgkin lymphoma

Liso-Cel by Disease State

Lisocabtagene maraleucel (liso-cel; JCAR017; CD19 CAR T) in Lymphoma

  • Phase 2 Lymphoma Agressive large B-cell lymphoma: Relapsed/refractory

Rationale for Clinical Development

Preclinical studies have suggested that CAR T cells directed against CD19 demonstrate antitumor activity against lymphoma cells in mouse models.11,12

 

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.

 

References

  1. Abramson AS, et al. Oral presented at ASH 2017 [abstract 581].
  2. NCI Drug Dictionary. https://www.cancer.gov/publications/dictionaries/cancerdrug?cdrid=778386. Accessed May 5, 2018.
  3. Scheuermann RH and Racila E. Leuk Lymphoma. 1995;18:385-397. PMID: 8528044
  4. Wang K, et al. MAbs. 2012;4:571-577. PMID: 23109152
  5. Maude SL, et al. Blood. 2015;125:4017-4023. PMID: 25999455
  6. Dotti G, et al. Immunol Rev. 2014;257:107-126. PMID: 24329793
  7. Bridgeman JS, et al. Clin Exp Immunol. 2014;175:258-267. PMID: 24116999
  8. Davila ML, et al. Int J Hematol. 2014;99:361-371. PMID: 24311149
  9. Maus MV and June CH. Clin Cancer Res. 2016;22:1875-1884. PMID: 27084741
  10. Maloney D, et al. Blood. 2017;130(suppl 1)[abstract 1552].
  11. Cheadle EJ, et al. J Immunol. 2010;184:1885-1896. PMID: 20089697
  12. Kochenderfer JN, et al. Blood. 2010;116:3875-3886. PMID: 20631379