Targeting neoantigens to augment antitumour immunity
Open accessAbstract
The past decade of cancer research has been marked by a growing appreciation of the role of immunity in cancer. Mutations in the tumour genome can cause tumours to express mutant proteins that are tumour specific and not expressed on normal cells (neoantigens). These neoantigens are an attractive immune target because their selective expression on tumours may minimize immune tolerance as well as the risk of autoimmunity. In this Review we discuss the emerging evidence that neoantigens are recognized by the immune system and can be targeted to increase antitumour immunity. We also provide a framework for personalized cancer immunotherapy through the identification and selective targeting of individual tumour neoantigens, and present the potential benefits and obstacles to this approach of targeted immunotherapy.
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Sipuleucel-T provides a survival benefit in castrate-resistant metastatic prostate cancer, shown in a large randomized controlled trial.
“sipuleucel-T, a cancer vaccine for castrate-resistant metastatic prostate cancer, has conclusively provided a survival benefit in a large RCT131.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [131]
The section on therapeutic approaches for targeting predicted neoantigens states that sipuleucel-T has conclusively demonstrated a survival benefit in castration-resistant metastatic prostate cancer. Our copy does not state that the benefit was shown in a large randomized controlled trial; its reference list identifies a sipuleucel-T study but gives no trial design or size. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBecause mutation-associated neoantigens are absent from non-malignant cells, vaccines targeting them might avoid central or peripheral tolerance and produce robust immune responses.
“Given that mutation-associated neoantigens are not expressed on any non-malignant cell, vaccines targeting them might avoid central or peripheral tolerance mechanisms, resulting in robust immune responses131.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [131]
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Self-citation
- Authors
- Yarchoan, M., Johnson, B. A., Lutz, E. R., Laheru, D. A., & Jaffee, E. M.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Jaffee, Elizabeth M.
- Venue
- Nature Reviews Cancer
- Published
- 2017-02-24
- Volume
- 17
- Issue
- 4
- Pages
- 209-222
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC5575801
- OpenAlex
- W2590497374
- Cited by
- 997
- References
- 166
- Citations by year
- 2026: 47 · 2025: 61 · 2024: 94 · 2023: 118 · 2022: 137 · 2021: 158 · 2020: 125 · 2019: 107 · 2018: 96 · 2017: 53
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-24)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins University
- National Cancer Institute (R01CA197296, T32CA009071, P30CA006973)
- Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- neoantigens, antitumor immunity, personalized cancer immunotherapy, tumor-specific antigens, tumour mutations, immune tolerance, autoimmunity, targeted immunotherapy, tumor immunology
- MeSH terms
- Animals, Antigens, Neoplasm, Humans, Immunotherapy, Mutation, Neoplasms, T-Lymphocytes, Tumor Escape, Adoptive Transfer, Precision Medicine, Tumor Microenvironment
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