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Neoantigen Burden – Meaning & Role in Immunotherapy

Neoantigen burden refers to the number of tumor-specific antigens present on cancer cells. It is a key biomarker for predicting the effectiveness of cancer immunotherapies.

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Things worth knowing about "Neoantigen burden"

Neoantigen burden refers to the number of tumor-specific antigens present on cancer cells. It is a key biomarker for predicting the effectiveness of cancer immunotherapies.

What is Neoantigen Burden?

The neoantigen burden describes the total number of tumor-specific protein alterations that are displayed on the surface of cancer cells. These altered proteins, known as neoantigens, arise from genetic mutations in tumor cells and are recognized as foreign by the immune system. The higher the neoantigen burden, the more potential targets the immune system has to attack the tumor.

How Neoantigens Are Formed

Neoantigens are generated when mutations in the DNA of a tumor cell lead to the production of altered proteins. These proteins are presented on the cell surface via the MHC complex (major histocompatibility complex). Because the immune system does not recognize these altered structures as self, specific T cells can be activated to destroy the tumor cells.

Point mutations (changes in individual DNA bases)
Insertions or deletions in the genome
Chromosomal rearrangements
Alterations caused by viruses or other external factors

Significance as a Biomarker

Neoantigen burden is considered an important predictive biomarker in oncology. Studies have shown that tumors with a high neoantigen burden often respond better to immune checkpoint inhibitors. These drugs, such as PD-1 or CTLA-4 blockers, release the brakes on the immune system and allow a stronger immune response against the tumor.

A high neoantigen burden is frequently found in tumor types with elevated mutation rates, including:

Malignant melanoma (skin cancer)
Non-small cell lung carcinoma (NSCLC)
Colorectal cancer with microsatellite instability (MSI-H)
Bladder carcinoma

Relationship to Tumor Mutational Burden

Neoantigen burden is closely related to tumor mutational burden (TMB). TMB measures the total number of somatic mutations in tumor tissue, while neoantigen burden specifically captures those mutations that actually lead to immunogenically presented proteins. Both parameters are increasingly used to select patients for immunotherapy.

Diagnostics and Measurement

Neoantigen burden is determined using molecular genetic methods:

Next-generation sequencing (NGS): Comprehensive sequencing of the tumor genome to identify mutations
Bioinformatic analysis: Prediction of which mutations lead to the formation of immunogenic neoantigens
HLA typing: Determination of the individual MHC molecules of the patient, as neoantigen presentation is HLA-dependent

Clinical Relevance and Treatment Planning

In personalized cancer medicine, neoantigen burden plays a growing role. It serves not only as a basis for selecting appropriate immunotherapies, but also for the development of individualized neoantigen vaccines (cancer vaccines). In this approach, the specific neoantigens of a patient are identified and used as a vaccine to trigger a targeted immune response against the tumor. Such personalized cancer vaccines are currently being evaluated in clinical trials and show promising results.

References

Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69-74. doi:10.1126/science.aaa4971
Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. New England Journal of Medicine. 2017;377(25):2500-2501.
World Health Organization (WHO). Cancer Immunotherapy: Current Developments and Future Directions. WHO Technical Report, 2022.

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