Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Immune checkpoint blockage (ICB) therapy has demonstrated significant clinical benefits in cancer treatment.
• Antitumor cytotoxic T cells can be reinvigorated or enhanced by ICB, highlighting their therapeutic potential.
• Neoantigens, derived from tumor somatic mutations, are considered superior immune targets compared to self-antigens.

Purpose of the Study:

• To review recent advancements in the identification of neoantigens.
• To discuss preclinical and clinical studies utilizing neoantigens in cancer therapy.
• To highlight challenges and future directions for clinical applications of neoantigen-based immunotherapies.

Main Methods:

• Immunogenomic and immunopeptidomic approaches are employed for neoantigen identification.
• Analysis of tumor mutation burden (TMB) and neoantigen loads as indicators for immunotherapy response.
• Evaluation of mismatch repair-deficient tumors' susceptibility to T cell-mediated eradication with ICB.

Main Results:

• Neoantigen identification has revealed clinical relevance, with TMB and neoantigen load potentially predicting immunotherapy outcomes.
• Mismatch repair-deficient tumors show promise for eradication via T cells during ICB treatment.
• Vaccines and adoptive T-cell transfer targeting neoantigens represent promising innovative therapeutic strategies.

Conclusions:

• Neoantigen-based immunotherapies, including vaccines and adoptive T-cell transfer, offer innovative strategies for cancer treatment.
• Further research is crucial to identify optimal neoantigen epitopes for enhanced therapeutic efficacy.
• Addressing current challenges is essential for the successful clinical translation of neoantigen-targeted therapies.