[Identification of neoantigens and development of antigen-specific immunotherapy]

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Somatic mutations in cancer cells generate neoantigens, which are foreign to the host immune system.
• Neoantigens possess high immunogenicity, capable of eliciting specific T-cell responses against cancer.
• These characteristics position neoantigens as promising targets for novel anti-cancer immunotherapies.

Purpose of the Study:

• To review the methods for identifying neoantigens.
• To discuss the role of neoantigens in anti-cancer immunotherapy.
• To highlight the potential of neoantigens in hematological malignancies.

Main Methods:

• Identification of non-synonymous mutations via whole exome and RNA sequencing.
• In silico prediction of neoantigens using MHC ligand prediction algorithms.
• Verification of T-cell responses to candidate neoantigens using tumor-infiltrating T cells or peripheral blood mononuclear cells.

Main Results:

• Neoantigens derived from frameshift mutations and fusion genes are prevalent in hematological malignancies.
• A shared neoantigen from nucleophosmin I frameshift mutation in acute myeloid leukemia demonstrated specific immune responses in vitro and in vivo.
• These findings underscore the therapeutic potential of neoantigens in specific cancer types.

Conclusions:

• Neoantigens represent a significant avenue for developing targeted anti-cancer immunotherapies.
• Further research is needed to address challenges for the clinical application of neoantigen-based therapies.
• Neoantigens hold promise for treating hematological malignancies, particularly those with high rates of frameshift mutations and fusion genes.