ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Adoptive transfer of human papillomavirus E7-specific CTL enhances tumor chemoresponse through the perforin/granzyme-mediated pathway.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 31 citations in OpenAlex.
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- Vaccines for established cancer: overcoming the challenges posed by immune evasion.Nature reviews. Cancer · 2016Review
- Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus.Journal of clinical medicine · 2015Review
- DNA vaccines, electroporation and their applications in cancer treatment.Human vaccines & immunotherapeutics · 2015Review
- Biological basis for increased sensitivity to radiation therapy in HPV-positive head and neck cancers.BioMed research international · 2014Review
- Intranasal immunization with a flagellin-adjuvanted peptide anticancer vaccine prevents tumor development by enhancing specific cytotoxic T lymphocyte response in a mouse model.Clinical and experimental vaccine research · 2013Article
- DNA vaccines targeting human papillomavirus-associated diseases: progresses in animal and clinical studies.Clinical and experimental vaccine research · 2013Article
- Intratumoral electroporation of IL-12 cDNA eradicates established melanomas by Trp2(180-188)-specific CD8+ CTLs in a perforin/granzyme-mediated and IFN-γ-dependent manner: application of Trp2(180-188) peptides.Cancer immunology, immunotherapy : CII · 2012Article
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adoptive cytotoxic T lymphocyte (CTL) therapy has an important implication in treating cancer patients. Here, we investigate whether adoptive transfer of human papillomavirus (HPV) E7-specific CTL can enhance tumor chemoresponse using an established cervical cancer animal model. Cisplatin-based chemotherapy plus CTL therapy showed an improved therapeutic effectiveness, along with antitumor protective responses to a parental tumor cell rechallenge. Cisplatin treatment dose-dependently increased the expression of Fas, intercellular adhesion molecule (ICAM)-1, and major histocompatibility complex (MHC) class I antigens (Ags) on tumor cells in vitro. However, CTL-expressing FasL failed to improve antitumor activity in vitro and in animals, resulting from nonfunctional Fas expressed on tumor cells. In contrast, ethylene glycol tetraacetic acid (EGTA) treatment blocked increased sensitivity of cisplatin-treated tumor cells to CTL-mediated killing in vitro, suggesting an important role of the perforin/granzyme-mediated pathway for improved therapeutic effectiveness. This notion was further confirmed by perforin knockout animal studies. Thus, this study shows that (i) modulation of Ag (Fas, ICAM-1) expression by tumor cells has little effect on their increased sensitivity to CTL-mediated killing, (ii) improved therapeutic effectiveness is mediated mainly through the perforin/granzyme-mediated tumor killing pathway, and (iii) a combination of chemotherapy and adoptive E7-specific CTL transfer augments antitumor therapeutic activity in vivo. This finding may have important implications for treating HPV-associated cervical cancer.
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