Development of a T-cell Receptor Mimic Antibody against Wild-Type p53 for Cancer Immunotherapy
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Abstract
The tumor suppressor p53 is widely dysregulated in cancer and represents an attractive target for immunotherapy. Because of its intracellular localization, p53 is inaccessible to classical therapeutic monoclonal antibodies, an increasingly successful class of anticancer drugs. However, peptides derived from intracellular antigens are presented on the cell surface in the context of MHC I and can be bound by T-cell receptors (TCR). Here, we report the development of a novel antibody, T1-116C, that acts as a TCR mimic to recognize an HLA-A*0201–presented wild-type p53 T-cell epitope, p5365–73(RMPEAAPPV). The antibody recognizes a wide range of cancers, does not bind normal peripheral blood mononuclear cells, and can activate immune effector functions to kill cancer cells in vitro. In vivo, the antibody targets p5365–73 peptide–expressing breast cancer xenografts, significantly inhibiting tumor growth. This represents a promising new agent for future cancer immunotherapy. Cancer Res; 77(10); 2699–711. ©2017 AACR.
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Li and Banham's group generated a TCR mimic antibody, T1-116C, that recognizes a p53-derived epitope selectively displayed on MHC class I only by cancer cells, inducing tumor regression in mice with breast cancer xenografts.
“In 2017, Li and Banham’s group innovatively generated a TCR mimic antibody, T1-116C (259), that recognize a p53-derived epitope selectively displayed on MHC class I only by cancer cells, inducing tumor regression in mice with breast cancer xenografts.607”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [607]
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- Authors
- Li, D., Bentley, C., Anderson, A., Wiblin, S., Cleary, K. L. S., Koustoulidou, S., Hassanali, T., Yates, J., Greig, J., Nordkamp, M. O., Trenevska, I., Ternette, N., Kessler, B. M., Cornelissen, B., Cragg, M. S., & Banham, A. H.
- Affiliations
- John Radcliffe Hospital (GB)
- Southampton General Hospital (GB)
- University of Oxford (GB)
- Corresponding author
- Li, Demin
- Banham, Alison H.
- ORCID
- Venue
- Cancer Research
- Published
- 2017-05-14
- Volume
- 77
- Issue
- 10
- Pages
- 2699-2711
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2603085196
- Cited by
- 38
- References
- 57
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 2
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Cancer Research UK (A10702)
- Medical Research Council (A10702)
- Biotechnology and Biological Sciences Research Council (12050)
- CRUK (A20537)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- p53, cancer immunotherapy, wild-type p53, T cell epitopes, HLA-A*0201, MHC class I antigen presentation, intracellular antigens, breast cancer xenografts, tumor growth inhibition
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Disease Models, Animal, Female, Humans, Immunotherapy, Neoplasms, Protein Binding, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, HLA-A2 Antigen, Immunophenotyping, Tumor Suppressor Protein p53, Molecular Mimicry, Epitopes, T-Lymphocyte, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Mice, Protein Multimerization
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