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Mutation-Derived Neoantigens for Cancer Immunotherapy
John C Castle1, Mohamed Uduman1, Simarjot Pabla1
1Agenus Inc., Lexington, MA, United States.
Frontiers in Immunology
|August 24, 2019
Summary
Tumor mutations create neoantigens that T cells target. Immunotherapies like vaccines and adoptive cell therapy (ACT) harness these neoantigens to enhance anti-tumor immune responses.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Tumor cells present mutation-derived neoantigens, recognized by T cells.
- Cancer immunotherapies aim to enhance T-cell-mediated tumor destruction.
- Neoantigens are key targets for cancer vaccines and adoptive cell therapy (ACT).
Purpose of the Study:
- To review the spectrum of mutations across various cancer indications.
- To identify variations in mutation prevalence within and between cancer subtypes.
- To examine recurring mutation neoantigens for potential immunotherapy applications.
Main Methods:
- Analysis of publicly funded tumor genome profiling data.
- Comparison of mutation frequencies across different cancer types and subtypes.
- Identification of prevalent neoantigens for vaccine and ACT development.
Main Results:
- Basal and HER2+ breast tumors show higher mutation rates than luminal A/B.
- HPV-negative head and neck tumors have more mutations than HPV-positive.
- Lung adenocarcinomas in smokers exhibit significantly more mutations than in non-smokers.
Conclusions:
- Mutation neoantigen profiles vary significantly across cancer indications and subtypes.
- Recurring neoantigens present opportunities for 'off-the-shelf' immunotherapies.
- Understanding mutation landscapes is crucial for developing effective neoantigen-targeted therapies.
