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Cancer Target Rationale

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and cancer-testis antigen 2 L antigen family member 1 isoform A(LAGE-1a) are homologous highly immunogenic cancer-testis antigens that can elicit humoral and cellular immune responses in cancer patients.1,2

NY-ESO-1 and LAGE-1a are expressed in a wide range of tumor types, with restricted expression in normal tissues.1

Overview

Letetresgene autoleucel (lete-cel; GSK3377794) is a genetically modified autologous T cell that expresses a TCR with greater affinity for NY-ESO-1.1

Lete-cel is being investigated as a monotherapy and in combination with pembrolizumab in NY-ESO-1– and/or LAGE-1a–positive solid tumors, including NSCLC, myxoid/round cell liposarcoma, and synovial sarcoma.3

References

  1. Thomas R, Al-Khadairi G, Roelands J, et al. NY-ESO-1 based immunotherapy of cancer: current perspectives. Front Immunol. 2018;9:947. doi:10.3389/fimmu.2018.00947.
  2. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914-921.
  3. ClinicalTrials.gov. Accessed September 21, 2021. www.clinicaltrials.gov/