Fiche publication
Date publication
octobre 2025
Journal
Cancer immunology research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
,
Dr BINDA Delphine
,
Pr BORG Christophe
,
Pr GARNACHE-OTTOU Francine
,
Dr GODET Yann
,
Mme BOUARD Adeline
,
Dr VIENOT Angélique
,
Dr ASGAROV Kamal
,
Dr LOYON Romain
,
Dr KROEMER Marie
Tous les auteurs :
Ben Khelil M, Fredon M, Adib N, Bouard A, Perchaud M, Abdeljaoued S, Mantion CF, Asgarov K, Guillaume P, Spehner L, Seffar E, Labesse M, Vienot A, Mougey V, Gonçalves-Venturelli M, Bobisse S, Harari A, Jandus C, Garnache-Ottou F, Binda D, Adotévi O, Godet Y, Kroemer M, Borg C, Loyon R
Lien Pubmed
Résumé
Aberrant expression of the oncogene SALL4 is associated with stemness, more aggressive cancer phenotype, and reduced patient survival in various tumor types making SALL4 a potential target for cancer immunotherapy. We conducted a transcriptional analysis of SALL4 expression in colorectal cancer (CRC) tissues and demonstrated that SALL4 was overexpressed in primary tumor and paired liver metastasis. Then, we identified the SALL4-derived S9V peptide as a naturally processed peptide that induced specific CD8+ T-cell responses from the peripheral blood of gastrointestinal cancer patients whereas no responses were observed for the peripheral blood of healthy donors. Thereafter, we isolated a SALL4-specific T-cell receptor (TCR) that recognized this peptide in the most common HLA molecule in the Caucasian population, HLA-A2, and used this to develop TCR-engineered T cells. In vitro analysis showed that SALL4 TCR-redirected primary CD8+ T cells exhibited cytotoxic effects against SALL4-expressing tumor cells and produced effector cytokines. In vivo, SALL4-TCR T cells significantly reduced tumor growth and improved survival of tumor-bearing mice. Moreover, SALL4-TCR T cells displayed no toxicity against hematopoietic stem cells. Thus, we conclude that T cells engineered to express a SALL4-specific TCR have the potential to be effective as immunotherapy for solid cancers and pave the way for further clinical development.
Référence
Cancer Immunol Res. 2025 10 20;:
