Neoepitopes are a class of

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

(MHC) bounded peptides. They represent the

antigenic determinant An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

s of

neoantigen Tumor antigen is an antigenic substance produced in tumor cells, i.e., it triggers an immune response in the host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential candidates for use in c ...

s. Neoepitopes are recognized by the immune system as targets for T cells and can elicit immune response to cancer.

Description

Epitopes, also referred to as antigenic determinants, are parts of an antigen that are recognized by the immune system. A neoepitope is an epitope the immune system has not encountered before. Therefore it is not subject to tolerance mechanisms of the immune system. As the mutant gene product is only expressed in tumors and is not found in non-cancerous cells, neoepitopes may evoke a vigorous T cell response. Tumor Mutational Burden (TMB, the number of mutations within a targeted genetic region in the cancerous cell's DNA) correlates with the number of neoepitopes, and have been suggested to correlate with patient survival post immunotherapy, although the findings about the neoantigen/immunogenicity association are disputed. Neoepitopes arise from post-translational modifications. The mRNA translates information from the DNA into

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

composed of 20 standard amino acids and then proteins. Several of the standard amino acids can be posttranslationally modified by enzymatic processes, or can be altered through spontaneous (nonenzymatic)

biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

reactions. There is increasing evidence that immune recognition of neoepitopes produced by cancer-specific mutations is a key mechanism for the induction of immune-mediated tumor rejection. Opportunities for therapeutic targeting of cancer specific neoepitopes are under investigation.

As target for immunotherapy

Cancer is a patient-specific disease, and no two tumors are alike. Thus, the immunogenicity of each tumor is unique. A novel strategy against cancer is epitope selection for mutanome-directed

individualized cancer immunotherapy Individualized cancer immunotherapy, also referred to as individualized immuno-oncology, is a novel concept for therapeutic cancer vaccines that are truly personalized to a single individual. The human immune system is generally able to recognize ...

. Individualized cancer immunotherapy leverages the adaptive immune system by targeting T cells to tumor cells that have a tumor specific mutant antigen (

) with neoepitopes recognized by a receptor on T cells. One challenge is to identify the neoepitopes that trigger a suitable immune response, that is, to find out which neoepitopes in the individual tumor are highly immunogenic.

Cancer vaccines

Individualized cancer immunotherapy includes vaccination with tumor mutation-derived neoepitopes. The concept is based on a mapping of the tumor-specific individual mutanome with identification of a range of suitable neoepitopes for a patient-specific vaccine. It is expected that the neoepitopes in the vaccine will trigger T cell responses to the specific cancer. For the concept of individualized cancer vaccination first data are available.

References

{{reflist Medical genetics Biotechnology Applied genetics Genomics Immunology Cancer vaccines