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- Title
Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy.
- Authors
Nobuoka, Daisuke; Yoshikawa, Toshiaki; Takahashi, Mari; Iwama, Tatsuaki; Horie, Kazutaka; Shimomura, Manami; Suzuki, Shiro; Sakemura, Noriko; Nakatsugawa, Munehide; Sadamori, Hiroshi; Yagi, Takahito; Fujiwara, Toshiyoshi; Nakatsura, Tetsuya
- 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)-A*02:01-restricted glypican-3 (FVGEFFTDV) and cytomegalovirus (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-3 and cytomegalovirus 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 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.
- Subjects
ANTIGENS; IMMUNOTHERAPY; CYTOTOXIC T lymphocyte-associated molecule-4; CANCER treatment; CANCER patients; CLINICAL trials
- Publication
Cancer Immunology, Immunotherapy, 2013, Vol 62, Issue 4, p639
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-012-1366-6