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Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine

Mona O Mohsen1,2,3, Monique Vogel2, Carsten Riether4

  • 1Nuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford, United Kingdom.

Frontiers in Immunology
|June 4, 2019
PubMed

Insights

Personalized cancer vaccines targeting neoantigens show promise. Combining mutated and germline antigens in a novel nano-vaccine platform significantly enhanced therapeutic efficacy against melanoma.

Area of Science:

  • Oncology
  • Immunology
  • Nanotechnology

Background:

  • Personalized cancer vaccines offer a promising therapeutic strategy.
  • Targeting tumor-specific neoantigens is generally more effective than targeting germline antigens.
  • Identifying and utilizing neoantigens for vaccination presents practical challenges.

Purpose of the Study:

  • To investigate if two neoantigens are sufficient for therapeutic efficacy.
  • To determine if combining germline and mutated antigens enhances vaccine effectiveness.
  • To develop and evaluate a personalized cancer nano-vaccine platform.

Main Methods:

  • Developed a personalized cancer nano-vaccine platform using virus-like particles (VLPs) loaded with toll-like receptor ligands.
  • Generated three sets of multi-target vaccines (MTVs): germline epitopes (GL-MTV), mutated epitopes (Mutated-MTV), and a combination (Mix-MTV).
  • Utilized Cu-free click chemistry for peptide-VLP coupling for potential bedside production.

Main Results:

  • Both germline and mutated epitopes demonstrated protective immunity against B16F10 murine melanoma.
  • The combination vaccine (Mix-MTV) achieved the best therapeutic effect.
  • The nano-vaccine platform demonstrated potential for clinical translation.

Conclusions:

  • A combination of germline and mutated epitopes provides superior therapeutic efficacy in personalized cancer vaccines.
  • The developed VLP-based nano-vaccine platform is adaptable for bedside production, facilitating clinical translation.
  • Targeting both neoantigens and germline antigens represents a viable strategy for enhancing cancer immunotherapy.
Keywords:
germlinemelanomamutatedneoantigenpersonalizedvaccinevirus-like particles

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