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Updated: Nov 22, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens
Robin Minati1,2, Claude Perreault2,3, Pierre Thibault2,4
1École Normale Supérieure de Lyon, Université Claude Bernard Lyon I, Université de Lyon, Lyon, France.
Abstract:
The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.
Insights
Identifying novel tumor-specific antigens (TSAs) is crucial for developing effective cancer immunotherapies. Exploring non-canonical protein regions expands the potential targets for T cell-mediated antitumor responses.
Area of Science:
- Immunology
- Oncology
- Proteogenomics
Background:
- Proteogenomic methods have advanced the discovery of tumor-specific antigens (TSAs).
- TSAs offer opportunities for novel antitumoral immunotherapies targeting T cell responses.
- Current TSA identification primarily focuses on mutated antigens from coding exons, yielding limited candidates.
Purpose of the Study:
- To review potential sources of TSAs and their cancer-specific expression mechanisms.
- To explore the expansion of targetable TSAs from non-canonical open reading frames.
- To propose TSA families potentially enriched in specific cancer types.
Main Methods:
- Literature review of proteogenomic detection methods for TSAs.
- Analysis of antigen expression mechanisms in cancer cells.
- Evaluation of non-canonical protein regions as sources for TSAs.
Main Results:
- Improved proteogenomics accelerates TSA identification.
- Non-canonical open reading frames represent a promising, largely untapped source of TSAs.
- Cancer heterogeneity suggests TSA families may be specific to certain tumor types.
Conclusions:
- Expanding TSA discovery beyond canonical exons is vital for cancer immunotherapy.
- Understanding cancer-specific expression mechanisms is key to developing effective immunotherapies.
- Targeting specific TSA families could enhance treatment efficacy for distinct cancer types.
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