Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: A potential option for improvement in antigen-specific cancer immunotherapy

Daisuke Nobuoka, Toshiaki Yoshikawa, Mari Takahashi, Tatsuaki Iwama, Kazutaka Horie, Manami Shimomura, Shiro Suzuki, Noriko Sakemura, Munehide Nakatsugawa, Hiroshi Sadamori, Takahito Yagi, Toshiyoshi Fujiwara, Tetsuya Nakatsura

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Antigen-specific cancer immunotherapy is a promising strategy for improving cancer treatment. Recently, many tumor-associated antigens and their epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the density of endogenously presented antigen-derived peptides on tumor cells is generally sparse, resulting in the inability of antigen-specific CTLs to work effectively. We hypothesize that increasing the density of an antigen-derived peptide would enhance antigen-specific cancer immunotherapy. Here, we demonstrated that intratumoral peptide injection leads to additional peptide loading onto major histocompatibility complex class I molecules of tumor cells, enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, human leukocyte antigen (HLA)-A02:01-restricted glypican-3144-152 (FVGEFFTDV) and cytomegalovirus495-503 (NLVPMVATV) peptide-specific CTLs showed strong activity against all peptide-pulsed cell lines, regardless of whether the tumor cells expressed the antigen. In in vivo studies using immunodeficient mice, glypican-3144-152 and cytomegalovirus 495-503 peptides injected into a solid mass were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of ovalbumin 257-264 peptide (SIINFEKL) was effective for tumor growth inhibition and survival against ovalbumin-negative tumors without adverse reactions. Moreover, we demonstrated an antigen-spreading effect that occurred after intratumoral peptide injection. Intratumoral peptide injection enhances tumor cell antigenicity and may be a useful option for improvement in antigen-specific cancer immunotherapy against solid tumors.

Original languageEnglish
Pages (from-to)639-652
Number of pages14
JournalCancer Immunology, Immunotherapy
Volume62
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Antigen
  • Cytotoxic T lymphocyte
  • Immunotherapy
  • Intratumoral peptide injection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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