Characterization of a novel T cell-engaging bispecific antibody for elimination of L1CAM-positive tumors - 27/04/24
Abstract |
Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | A novel L1CAM-targeted T cell engaging bispecific antibody that has been developed based on the IgG-(L)-ScFv structure. |
• | CE7-TCE acted as a cell-engager to redirect T cells to tumor cells, and effectively induce tumor killing both in vitro and in vivo. |
• | CE7-TCE exhibited a better anti-tumor efficacy after blocking PD1/PD-L1 immunosuppression in combination with Pembrolizumab. |
Keywords : Neural cell adhesion molecule L1 (L1CAM), T cell-engaging bispecific antibody, Immunotherapy, Anti-PD-1 antibody, Combination therapy
Plan
Vol 174
Article 116565- mai 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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