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Tumor Antigens beyond the Human Exome
Lisabeth Emilius1,2,3,4, Franziska Bremm1,2,3,4, Amanda Katharina Binder1,2,3,4
1Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Abstract:
With the advent of immunotherapeutics, a new era in the combat against cancer has begun. Particularly promising are neo-epitope-targeted therapies as the expression of neo-antigens is tumor-specific. In turn, this allows the selective targeting and killing of cancer cells whilst healthy cells remain largely unaffected. So far, many advances have been made in the development of treatment options which are tailored to the individual neo-epitope repertoire. The next big step is the achievement of efficacious "off-the-shelf" immunotherapies. For this, shared neo-epitopes propose an optimal target. Given the tremendous potential, a thorough understanding of the underlying mechanisms which lead to the formation of neo-antigens is of fundamental importance. Here, we review the various processes which result in the formation of neo-epitopes. Broadly, the origin of neo-epitopes can be categorized into three groups: canonical, noncanonical, and viral neo-epitopes. For the canonical neo-antigens that arise in direct consequence of somatic mutations, we summarize past and recent findings. Beyond that, our main focus is put on the discussion of noncanonical and viral neo-epitopes as we believe that targeting those provides an encouraging perspective to shape the future of cancer immunotherapeutics.
Insights
Cancer immunotherapies are advancing with neo-epitope-targeted treatments. Understanding neo-antigen formation, including canonical, noncanonical, and viral types, is crucial for developing effective "off-the-shelf" cancer vaccines.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Immunotherapeutics represent a significant advancement in cancer treatment.
- Neo-antigen-targeted therapies offer tumor-specific cancer cell elimination, sparing healthy cells.
- Current treatments are personalized, but the development of
- off-the-shelf
- therapies is the next frontier.
Purpose of the Study:
- To review the mechanisms of neo-epitope formation in cancer.
- To categorize neo-epitopes into canonical, noncanonical, and viral origins.
- To highlight the potential of noncanonical and viral neo-epitopes for future cancer immunotherapeutics.
Main Methods:
- Literature review of existing research on neo-antigen formation.
- Categorization of neo-epitope origins based on their underlying mechanisms.
- Synthesis of findings related to canonical, noncanonical, and viral neo-epitopes.
Main Results:
- Neo-epitopes originate from three main categories: canonical (somatic mutations), noncanonical, and viral.
- Canonical neo-antigens arise directly from DNA mutations within tumor cells.
- Noncanonical and viral neo-epitopes represent promising targets for broader immunotherapeutic applications.
Conclusions:
- A comprehensive understanding of neo-epitope formation is essential for advancing cancer immunotherapy.
- Noncanonical and viral neo-epitopes offer significant potential for developing effective, broadly applicable
- off-the-shelf
- cancer immunotherapies.
- Targeting shared neo-epitopes is key to achieving efficacious universal cancer vaccines.
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