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ErbB2 genetic cancer vaccine in nonhuman primates: relevance of single nucleotide polymorphisms

Elena Fattori1, Luigi Aurisicchio, Immacolata Zampaglione

  • 1Istituto di Ricerca di Biologia Molecolare, Via Pontina, Pomezia, Italy. Elena_fattori@merck.com

Human Gene Therapy
|March 5, 2009
PubMed

Insights

This study developed a cancer vaccine targeting the Her2/neu tumor antigen in rhesus monkeys. The vaccine successfully elicited an immune response, highlighting the importance of tumor-associated antigen (TAA) polymorphisms in vaccine efficacy.

Area of Science:

  • Immunology
  • Oncology
  • Vaccinology

Background:

  • Aberrant Her2/neu expression drives epithelial carcinomas, making it a key target for immunotherapy.
  • Overcoming immunologic tolerance is crucial for effective cancer vaccine development against tumor-associated antigens (TAAs).

Purpose of the Study:

  • To develop methods for eliciting immunity against the Her2/neu TAA.
  • To construct DNA plasmids and adenoviral vectors for a Her2/neu cancer vaccine.
  • To investigate the impact of TAA polymorphisms on vaccine-induced immune responses.

Main Methods:

  • Isolated cDNA for rhesus monkey Her2/neu (RhErbB2) and created codon-optimized versions (RhErbB2OPT).
  • Constructed DNA plasmids and adenoviral vectors for genetic vaccination.
  • Vaccinated rhesus monkeys and analyzed immune responses, including epitope recognition.

Main Results:

  • Genetic vaccination effectively induced immune responses against RhErbB2 in rhesus monkeys.
  • Elicited immunity distinguished between self and nonself epitopes due to natural RhErbB2 polymorphisms.
  • Post-priming responses targeted nonself epitopes, while boosted responses cross-reacted with self epitopes.

Conclusions:

  • Her2/neu cancer vaccine strategies can elicit specific immune responses in animal models.
  • TAA polymorphisms significantly influence the nature and efficacy of vaccine-induced immunity.
  • Findings are relevant for designing cancer vaccines that account for TAA variations.

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