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Immunogenic mutanome of breast cancer: Advances, challenges and future directions in neoantigen-based immunotherapy

Almohanad A Alkayyal1, Niza H Saeedi1, Mamdouh S Moawadh1

  • 1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Saudi Arabia.

Advances in Clinical and Experimental Medicine : Official Organ Wroclaw Medical University
|August 1, 2025
PubMed

Insights

Neoantigen immunotherapies show promise for breast cancer (BC) treatment by targeting tumor mutations. Overcoming challenges like tumor heterogeneity is key to developing more effective, personalized BC therapies.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Breast cancer (BC) is a major global cause of cancer mortality, necessitating innovative treatments.
  • Neoantigen-based immunotherapy, leveraging tumor-specific mutations, presents a promising therapeutic avenue.
  • Current challenges include tumor heterogeneity and immune evasion, limiting clinical efficacy.

Purpose of the Study:

  • To review the current status of neoantigen-targeted immunotherapies for breast cancer.
  • To identify key obstacles hindering the broader clinical impact of these therapies.
  • To highlight emerging strategies for enhancing neoantigen immunotherapy efficacy.

Main Methods:

  • Systematic review of recent advancements in next-generation sequencing and computational immunopeptidomics.
  • Analysis of neoantigen identification and personalized vaccine design strategies.
  • Evaluation of immune-checkpoint blockade and combination regimens in breast cancer.

Main Results:

  • Next-generation sequencing and computational immunopeptidomics enable systematic tumor mutanome mapping and neoantigen identification.
  • Personalized vaccine design and immune-checkpoint blockade are advancing based on neoantigen discovery.
  • Intratumor heterogeneity and limited neoepitope immunogenicity remain significant clinical hurdles.

Conclusions:

  • Improved epitope-prediction algorithms, multi-epitope vaccines, and combination therapies are emerging solutions.
  • A comprehensive understanding of the immunogenic mutanome is crucial for developing durable breast cancer treatments.
  • Further research is expected to translate into more widely applicable and effective therapies for breast cancer patients.
Keywords:
breast cancerneoantigenspersonalized immunotherapytumor mutanometumor mutational burden (TMB)

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