53L10 T-cell engager tribody for immunotherapy of multiple solid tumors
4 affiliations
- 1Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”
- 2Ceinge-Biotecnologie Avanzate s.c.a.r.l.
- 3Chiome Bioscience Inc.
- 4European School of Molecular Medicine, University of Milan
Abstract
Cancer immunotherapy with immune checkpoint inhibitors (ICIs), i.e., antibodies targeting inhibitory ICs, such as PD-1, PD-L1, and CTLA-4, have successfully revolutionized cancer treatment. One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers that simultaneously bind with one arm to a tumor-associated antigen on tumor cells and with the other one to the CD3 complex on T cells to form a TCR-MHC-independent immune synapse. We previously generated four novel tribodies, tri-specific antibody derivative constructs, made up of a Fab targeting 5T4, an oncofetal tumor antigen expressed on several types of tumors, an scFv targeting CD3 on T cells, and an additional scFv specific for an immune checkpoint. In particular, the 53L10 tribody, targeting PD-L1, displayed the best binding properties and stronger anti-tumor activity in vitro and in vivo in mouse models. Here, we further investigated the anti-tumor potential of 53L10 by testing its effects on a panel of tumor cell types with a more aggressive profile, including gastric, pancreatic, prostate, ovarian, and epidermoid tumor cells. We found that 53L10 was very effective on these cells by inducing stronger T-cell activation and tumor cell lysis than the parental bi-specific 53P lacking an ICI. To further test its therapeutic potential, we also analyzed its stability and the effects on tumor T-cell infiltration in vivo on a mouse model. 53L10 was found to be stable after incubation in serum at 37 °C for 3 days and induced a more efficient and earlier increase in tumor tissues of both CD4 and CD8 T cells than the parental bi-specific 53P. These findings support further preclinical evaluation of 53L10 as a new tool for multiple solid tumor-targeted therapeutic approaches.
Related
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BibTeX
@article{passariello202653l10,
title = {{53L10 T-cell engager tribody for immunotherapy of multiple solid tumors}},
author = {Margherita Passariello and Martina Belardo and Toshikazu Inoue and Kentaro Kajiwara and Rosa Rapuano Lembo and Shu-ichi Hashimoto and Claudia De Lorenzo},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1934039},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1934039/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 53L10 T-cell engager tribody for immunotherapy of multiple solid tumors
AU - Margherita Passariello
AU - Martina Belardo
AU - Toshikazu Inoue
AU - Kentaro Kajiwara
AU - Rosa Rapuano Lembo
AU - Shu-ichi Hashimoto
AU - Claudia De Lorenzo
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1934039
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1934039/full
AB - Cancer immunotherapy with immune checkpoint inhibitors (ICIs), i.e., antibodies targeting inhibitory ICs, such as PD-1, PD-L1, and CTLA-4, have successfully revolutionized cancer treatment. One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers that simultaneously bind with one arm to a tumor-associated antigen on tumor cells and with the other one to the CD3 complex on T cells to form a TCR-MHC-independent immune synapse. We previously generated four novel tribodies, tri-specific antibody derivative constructs, made up of a Fab targeting 5T4, an oncofetal tumor antigen expressed on several types of tumors, an scFv targeting CD3 on T cells, and an additional scFv specific for an immune checkpoint. In particular, the 53L10 tribody, targeting PD-L1, displayed the best binding properties and stronger anti-tumor activity in vitro and in vivo in mouse models. Here, we further investigated the anti-tumor potential of 53L10 by testing its effects on a panel of tumor cell types with a more aggressive profile, including gastric, pancreatic, prostate, ovarian, and epidermoid tumor cells. We found that 53L10 was very effective on these cells by inducing stronger T-cell activation and tumor cell lysis than the parental bi-specific 53P lacking an ICI. To further test its therapeutic potential, we also analyzed its stability and the effects on tumor T-cell infiltration in vivo on a mouse model. 53L10 was found to be stable after incubation in serum at 37 °C for 3 days and induced a more efficient and earlier increase in tumor tissues of both CD4 and CD8 T cells than the parental bi-specific 53P. These findings support further preclinical evaluation of 53L10 as a new tool for multiple solid tumor-targeted therapeutic approaches.
SN - 1664-3224
ER -