PD-1 Targeted Antibody Discovery Using AI Protein Diffusion
Open accessPublished version of a preprint
Abstract
The programmed cell death protein 1 (PD-1, CD279) is an important therapeutic target in many oncological diseases. This checkpoint protein inhibits T lymphocytes from attacking other cells in the body and thus blocking it improves the clearance of tumor cells by the immune system. While there are already multiple FDA-approved anti-PD-1 antibodies, including nivolumab ( Opdivo ® from Bristol-Myers Squibb) and pembrolizumab ( Keytruda ® from Merck), there are ongoing efforts to discover new and improved checkpoint inhibitor therapeutics. In this study, we present multiple anti-PD-1 antibody fragments that were derived computationally using protein diffusion and evaluated through our scalable, in silico pipeline. Here we present nine synthetic Fv structures that are suitable for further empirical testing of their anti-PD-1 activity due to desirable predicted binding performance.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Watson, J. L., Juergens, D., Bennett, N. R., Trippe, B. L., Yim, J., Eisenach, H. E., Ahern, W., Borst, A. J., Ragotte, R. J., Milles, L. F., et al. (2022) · doi:10.1101/2022.12.09.519842 · Cited by 2,369 · see citing works
De novo design of protein structure and function with RFdiffusion
Watson, J. L., Juergens, D., Bennett, N. R., Trippe, B. L., Yim, J., Eisenach, H. E., Ahern, W., Borst, A. J., Ragotte, R. J., Milles, L. F., et al. (2023) · Nature · doi:10.1038/s41586-023-06415-8 · Cited by 2,325 · see citing works
Illuminating protein space with a programmable generative model
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Thera-SAbDab: the therapeutic structural antibody database
Raybould, M. I. J., Marks, C., Lewis, A. P., Shi, J., Bujotzek, A., Taddese, B., & Deane, C. M. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkz827 · Cited by 199 · cited 1× · see citing works
“Heavy and light chain sequences of 33 PD-1 targeting antibodies (Fv region only) were retrieved from the Therapeutic Structural Antibody Database (Thera-SAbDab) 18 on November 11, 2023.”
MethodFord, C. T., Yasa, S., Jacob Machado, D., White, R. A., & Janies, D. A. (2023) · Frontiers in Virology · doi:10.3389/fviro.2023.1172027 · Cited by 9 · see citing works
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- Authors
- Ford, C. T.
- Affiliations
- University of North Carolina at Charlotte (US)
- Corresponding author
- Ford, Colby T.
- ORCID
- Ford, Colby T.
- Venue
- Technology in Cancer Research & Treatment
- Publisher
- SAGE Publications
- Published
- 2024-01
- Volume
- 23
- Pages
- 15330338241275947-15330338241275947
- ISSN
- 1533-0338 (ISSN-L)
- 1533-0346
- PMC
- PMC11375674
- OpenAlex
- W4402239168
- Cited by
- 7
- References
- 6
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Technology in Cancer Research & Treatment (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- PD-1, anti-PD-1, protein diffusion, Fv fragment, immune checkpoint inhibitors, cancer immunotherapy, nivolumab, pembrolizumab, computational antibody design
- MeSH terms
- Antibodies, Artificial Intelligence, Humans, Immunoglobulin Variable Region, Neoplasms, Drug Design, Molecular Targeted Therapy, Programmed Cell Death 1 Receptor
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