Neoantigens are unique markers present on the surface of cancer cells. They represent altered proteins that arise from mutations within tumor DNA. These distinct markers play a significant role in the body’s immune response, acting as signals that can alert the immune system to the presence of cancerous cells. Because neoantigens are not found in normal tissues, they offer a specific target for immune cells, leading to a precise and effective attack on cancer. Their uniqueness makes them a focal point in the development of new cancer immunotherapies.
Understanding Neoantigens
Neoantigens are novel proteins or fragments that form from genetic mutations within cancer cells. Unlike normal self-antigens, neoantigens possess unique sequences not found in healthy cells. These new protein structures result from DNA alterations, including point mutations, insertions, deletions, and chromosomal rearrangements.
When genetic changes occur in tumor cells, they alter the amino acid sequence in produced proteins. This altered protein, when processed, generates peptide fragments distinct from normal proteins. These newly formed peptides are neoantigens, named from the Greek “neo,” meaning “new.” Their absence from healthy tissues makes them ideal immune targets.
Immune System Recognition
Once formed, neoantigens are processed inside cancer cells and displayed on their surface. This display occurs through specialized Major Histocompatibility Complex (MHC) molecules. MHC molecules present protein fragments from inside the cell, allowing immune cells to survey cellular contents.
The presentation of neoantigens by MHC molecules enables the immune system, particularly T cells, to recognize cancer cells as abnormal and foreign. T cells, a type of white blood cell, patrol the body, looking for non-self markers. When a T cell encounters an MHC molecule presenting a neoantigen, it recognizes this new peptide as foreign. This recognition triggers a specific immune response, prompting the T cell to destroy the cancer cell.
Targeting Cancer with Neoantigens
Leveraging neoantigens offers promising strategies for cancer treatment by enhancing the body’s immune attack against tumors. One strategy involves neoantigen vaccines, designed to prime or boost an immune response against these unique cancer markers. These vaccines introduce synthetic versions of identified neoantigens. Antigen-presenting cells, like dendritic cells, take up vaccine-delivered neoantigens and present them to T cells, activating and expanding a specific anti-tumor immune response.
Another approach uses adoptive cell therapies, where immune cells recognizing neoantigens are expanded outside the body and reinfused into the patient. This involves isolating tumor-infiltrating lymphocytes (TILs), immune cells naturally present within a tumor and often specific to neoantigens. These TILs are grown in large numbers in the laboratory and returned to the patient, where they seek out and destroy cancer cells expressing targeted neoantigens. The goal is to initiate or amplify a highly specific immune attack that minimizes harm to healthy tissues.
Developing Personalized Neoantigen Therapies
Neoantigens are highly patient-specific because each tumor’s unique set of mutations leads to a distinct neoantigen profile. This individuality necessitates a personalized approach to therapy. The process begins with a tumor biopsy from the patient. DNA from both tumor and healthy tissue is sequenced to identify genetic mutations in cancer cells.
Following sequencing, advanced bioinformatics analysis and prediction algorithms analyze the genetic data. These computational tools predict which identified mutations are most likely to generate neoantigens effectively presented by MHC molecules and recognized by the immune system. This analysis allows selection of the most potent and relevant neoantigens for each patient. The personalized nature of this process ensures therapies are precisely tailored to each patient’s tumor, leading to a highly targeted treatment strategy.