Cancer immunotherapy has rapidly advanced in recent years, offering powerful ways to help the body’s immune system detect and destroy cancer cells. One of the most important breakthroughs has been the development of immune checkpoint inhibitors, which block proteins like PD-1, PD-L1, and CTLA-4 to restore immune response against tumors. These therapies have already improved survival outcomes across various cancer types. Now attention is shifting to a new generation of treatment called personalized cancer vaccines. These vaccines are developed based on the unique genetic profile of a patient’s tumor and are designed to target neoantigens, which are mutated proteins found only on cancer cells. Unlike traditional tumor markers, neoantigens offer high specificity, helping the immune system attack cancer more precisely while sparing healthy tissue.
By focusing on neoantigens, personalized vaccines offer key benefits such as strong and precise T-cell activation, fewer side effects, and better alignment with the patient’s immune system through major histocompatibility complex (MHC) matching. Early-phase clinical trials have shown encouraging safety and efficacy results.¹ With mRNA platforms enabling faster development and customization, neoantigen-based vaccines are emerging as a powerful approach in precision oncology.
What Are Neoantigens?
Neoantigens are unique antigens produced by cancer cells due to genetic mutations. When a tumor’s DNA is altered through events like point mutations, insertions, deletions, or chromosomal changes, it can generate abnormal proteins. These proteins are broken down into peptide fragments and displayed on the surface of tumor cells. Since the immune system has never encountered these fragments before, it identifies them as foreign.
Because neoantigens originate from cancer-specific mutations and are absent from healthy tissue, they are ideal targets for immunotherapy. However, only a subset of mutations creates peptides that can bind to a patient's HLA molecules and activate T cells. These are the neoantigens of therapeutic interest. Identifying these enables scientists to design vaccines that train the immune system to recognize and attack cancer cells.
Global Advances in Neoantigen Cancer Vaccines
Countries worldwide are making significant progress in developing neoantigen-based cancer therapies. In China, firms like Genetron Health and GeneCast are targeting lung and liver tumors with personalized approaches. Moderna and Gritstone Bio in the U.S. are conducting trials for melanoma and glioblastoma. Meanwhile, Germany’s BioNTech is pioneering mRNA technologies with encouraging outcomes.¹ Together, these innovations reflect a strong international push toward precision cancer treatment.
How Do Neoantigens Arise?
Neoantigens stem from the genetic instability characteristic of tumors. As cancer grows, its DNA accumulates random mutations, some driven by environmental factors and others by internal errors. While many of these mutations are harmless passengers, a few act as drivers that fuel cancer progression. Both types can create neoantigens.
A single base change in DNA can alter a protein's amino acid sequence, resulting in a new peptide that the immune system perceives as a threat. Cancers with high mutation burdens, such as melanoma and lung cancer, often produce more neoantigens and respond better to immunotherapy. Additional sources of neoantigens include gene fusions, faulty RNA splicing, or mistranslated proteins. Each tumor's neoantigen profile is unique and shaped by its mutation landscape.
Shared vs Private Neoantigens
Neoantigens fall into two categories: private and shared. Private neoantigens are specific to an individual’s tumor, formed by unique mutations. These require fully personalized vaccine development. In contrast, shared neoantigens arise from common mutations in cancer driver genes like KRAS, TP53,...
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