For Which Types of Cancer Is a Personalized Vaccine Approach Being Evaluated? Mutation Burden Guide

Summary: A tumor’s mutation burden is associated with the number of neoantigens produced by that tumor and, consequently, with its response to immunotherapy. For this reason, tumors with high tumor mutational burden—such as melanoma, non-small cell lung cancer (NSCLC), and bladder cancer—are the groups most frequently studied for personalized multi-antigen vaccine approaches. In tumors with low tumor mutational burden, such as prostate cancer and certain subtypes of breast cancer, the expected response is more limited.

What Is the Relationship Between Mutation Burden and Neoantigens?

As the number of mutations in a tumor increases, the number of neoantigens that the immune system can recognize as “foreign” also tends to increase. The literature has demonstrated a correlation between a high neoantigen burden and the response to immune checkpoint inhibitors (such as anti-PD-1 therapies). This scientific basis also provides a framework for determining in which tumor groups personalized tumor lysate and mRNA neoantigen vaccines may be more rational.

Evaluation by Tumor Type

Tumors with a High Mutation Burden

Tumors such as melanoma, NSCLC, and bladder cancer exhibit high neoantigen diversity. This provides a basis for tumor lysate and mRNA vaccines to theoretically elicit a stronger T-cell response.

Tumors Showing a Partial Response to Immunotherapy

Tumors such as renal cell carcinoma, head and neck cancers, and MSI-high colorectal cancer are partially recognized by the immune system, but single-target approaches may sometimes prove insufficient. It is believed that multi-antigen strategies could create synergy in this group.

Heterogeneous Tumors

In tumors containing numerous subclones—such as glioblastoma, ovarian cancer, and pancreatic cancer—targeting a single antigen may be insufficient. The ability of tumor lysate to encompass the entire heterogeneous structure is considered a potential additional benefit in this group.

Patients with Residual/Minimal Disease Burden

In the adjuvant period following surgery or in cases of minimal residual disease after chemotherapy, where the tumor burden is low and the immune system is relatively unsuppressed, this is considered one of the most rational applications for such approaches.

Tumors with a Low Mutation Burden

In prostate cancer and certain subtypes of hormone-receptor-positive breast cancer, the number of neoantigens is relatively low; therefore, the expected response is anticipated to be more limited. (Note: Triple-negative breast cancer is excluded from this generalization because it has higher immunogenicity.)

Patients with Immunosuppression

Since dendritic cell function and T-cell response may be limited in patients who have undergone intensive chemotherapy or are on immunosuppressive therapy, this group is generally considered less suitable.

Why Is This Classification Important?

These categories are not a “treatment guarantee map” but rather a framework for scientific reasoning. Two patients with the same tumor type may have different tumor biology, mutation profiles, and immune statuses. Therefore, eligibility assessment must always be based on individual tumor analysis (RNA-seq, pathology, overall health status) and performed by a physician.

Frequently Asked Questions

Does this approach yield definitive results in tumors with a high mutation burden?

No. A high mutation burden theoretically increases the likelihood of a stronger response; however, this does not guarantee a specific outcome.

Is this approach never attempted in tumors with a low mutation burden?

It can be attempted, but the patient should be informed that the expected response may be limited; each case is evaluated on its own merits.

How is mutation burden measured?

It is assessed through RNA-seq or genomic sequencing analysis of tumor tissue; this analysis is typically performed on biopsy or surgical specimens.

This content is for informational purposes only; it does not diagnose, recommend treatment, or guarantee results. Be sure to consult a physician for a personalized evaluation.