The Japanese Journal of Pediatric Hematology / Oncology
Online ISSN : 2189-5384
Print ISSN : 2187-011X
ISSN-L : 2187-011X
Development of a novel immune checkpoint inhibitor suppressing both PD-1 and CTLA4 signals
Hiroki Nagase
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2019 Volume 56 Issue 3 Pages 331-333

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Abstract

The blockade of the PD-1 or CTLA-4 pathway is an attractive strategy for immuno-oncology (I-O) therapy for not only adults but also children. Here, we developed a novel therapeutic strategy using alkylating pyrrole-imidazole polyamide (CCC07-01) capable of the simultaneous downregulation of the expressions of the human PD-1, PD-L1 and CTLA-4 genes targeting a common recognition sequence of these genes. CCC07-01 significantly suppressed PD-1, PD-L1 and CTLA-4 mRNA and protein expressions and subsequently showed cell killing activity in several cancer cell lines, whereas it did not show cytotoxic effects on human non-tumorous cells. Fourteen days after CCC07-01 injection, we also observed a significant inhibition of tumor growth and a predominant induction of effector memory CD8 T cells in a study of a human xenograft colon carcinoma model in NGS mice, following the engraftment of human peripheral blood mononuclear cells (PBMCs). The blockade of both PD-1 and CTLA-4 pathways together with preferable cancer cell death induction by a single agent, CCC07-01, may be a promising anticancer therapeutic strategy.

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© 2019 The Japanese Society of Pediatric Hematology / Oncology
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