Enhancing antitumor response by efficiently generating large-scale TCR-T cells targeting a single epitope across multiple cancer antigens

• Published in: Cellular immunology 2024-05, Vol.399-400, p.104827-104827, Article 104827
• Main Authors: Amissah, Obed Boadi, Basnet, Rajesh, Chen, Wenfang, Habimana, Jean de Dieu, Baiden, Belinda Edwina, Owusu, Osei Asibey, Saeed, Babangida Jabir, Li, Zhiyuan
• Format: Article
• Language: English
• Subjects: Adoptive T cell therapy; Animals; Antigens, Neoplasm - immunology; Cancer testis antigen gene 1 (CTAG1); Cancer testis antigen gene 2 (CTAG2); Cell Line, Tumor; Epitopes - immunology; Epitopes, T-Lymphocyte - immunology; Humans; Immunotherapy; Immunotherapy, Adoptive - methods; Mice; Neoplasms - immunology; Neoplasms - therapy; Receptors, Antigen, T-Cell - immunology; Solid tumors; T-Lymphocytes - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2024.104827

•TCR-T cells are better expanded with xeno/sera-free medium.•Human AB serum is a good alternative to FBS as a supplement.•Beads-coated T-activator yields a better TCR-T cell effector function.•Targeting many antigens via a common epitope increases pMHC density to T cells.•Targeting multiple antigens by TCR-T cells improves their cancer-killing effect. The need to contrive interventions to curb the rise in cancer incidence and mortality is critical for improving patients’ prognoses. Adoptive cell therapy is challenged with quality large-scale production, heightening its production cost. Several cancer types have been associated with the expression of highly-immunogenic CTAG1 and CTAG2 antigens, which share common epitopes. Targeting two antigens on the same cancer could improve the antitumor response of TCR-T cells. In this study, we exploited an efficient way to generate large-fold quality TCR-T cells and also demonstrated that the common epitopes of CTAG1 and CTAG2 antigens provide an avenue for improved cancer-killing via dual-antigen-epitope targeting. Our study revealed that xeno/sera-free medium could expand TCR-T cells to over 500-fold, posing as a better replacement for FBS-supplemented media. Human AB serum was also shown to be a good alternative in the absence of xeno/sera-free media. Furthermore, TCR-T cells stimulated with beads-coated T-activator showed a better effector function than soluble T-activator stimulated TCR-T cells. Additionally, TCR-T cells that target multiple antigens in the same cancer yield better anticancer activity than those targeting a single antigen. This showed that targeting multiple antigens with a common epitope may enhance the antitumor response efficacy of T cell therapies.