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Related Concept Videos

Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.

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Updated: May 13, 2026

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A Framework for Comparing Mouse Neoantigen Immunogenicity.

Peter J Matulich1, Carly N Sprague1, Victoria P Schuster1

  • 1Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.

Biorxiv : the Preprint Server for Biology
|February 23, 2026
PubMed
Summary
This summary is machine-generated.

Comparing neoantigens in cancer immunotherapy is crucial. Peptide-MHC complex stability, not binding affinity, better predicts the effectiveness of cytotoxic CD8+ T cell responses in preclinical models.

Keywords:
Neoantigenantigen strengthimmunotherapypeptide-MHC stabilitypreclinical tumor models

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Area of Science:

  • Immunology
  • Cancer Research
  • T cell immunology

Background:

  • Cytotoxic CD8+ T cell responses against tumor neoantigens are vital for cancer immunotherapy success.
  • Preclinical mouse models are essential for studying these responses, but neoantigen choice can affect results.
  • Variations in neoantigen immunogenicity complicate the interpretation of tumor-intrinsic mechanisms.

Purpose of the Study:

  • To determine the relative immunogenicity of 25 common mouse tumor neoantigens.
  • To establish a benchmark for comparing neoantigens across different studies.
  • To provide a framework for contextualizing and comparing neoantigen immunogenicity.

Main Methods:

  • Assessed the immunogenicity of 25 commonly used mouse tumor-derived and model neoantigens.
  • Evaluated the correlation between *in silico* predicted MHC binding affinity and *in vivo* immunogenicity.
  • Experimentally measured peptide-MHC complex stability (Koff) and affinity (KD).

Main Results:

  • *In silico* predicted MHC binding affinity did not reliably predict *in vivo* immunogenicity.
  • Experimental measurement of peptide-MHC complex stability (Koff) strongly correlated with the magnitude of neoantigen-targeted vaccine responses *in vivo*.
  • Measured affinity (KD) showed a weaker correlation with *in vivo* immunogenicity compared to stability.

Conclusions:

  • Peptide-MHC complex stability is a more accurate predictor of neoantigen immunogenicity than binding affinity in preclinical models.
  • The study provides a reference library of neoantigen stability and a method for benchmarking new neoantigens.
  • This framework aids in the comparative interpretation of tumor-immune phenotypes and immunotherapy efficacy across studies.