Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells.

Journal for Immunotherapy of Cancer
Yuichi IidaMamoru Harada

Abstract

Mesenchymal stem/stromal cells (MSC) accumulate and reside in tumor sites. Taking advantage of this feature in anticancer therapy, immortalized murine MSC (iMSC) were genetically altered to produce chemokine (C-C motif) ligand 19 (iMSC/CCL19), which attracts dendritic cells (DC) and T lymphocytes. Thereafter, iMSC/CCL19 were examined for their therapeutic efficacy using a syngeneic CT26 colon carcinoma cell line. Co-injection of iMSC/CCL19 into mice significantly suppressed the in vivo growth of CT26 cells compared with that of CCL19-expressing immortalized fibroblasts (iFib/CCL19). This anticancer effect was not observed when injected in CT26-bearing nude mice. Co-injected iMSC/CCL19 survived longer than iFib/CCL19 in the tumor sites. In a therapeutic model, local injection of iMSC/CCL19 suppressed the tumor growth, and increased IFN (interferon)-γ+ CD8+ T cells and CCR7+ DC infiltration in tumor site was observed when treated with iMSC/CCL19, but not with iMSC. This antitumor effect was completely negated by depletion of CD4+ cells and partially negated by depletion of CD8+ cells. Furthermore, the antitumor effects induced by local injection of iMSC/CCL19 were augmented by additional therapy with anti-programmed death (PD)-li...Continue Reading

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Citations

Jan 2, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Anwar SalemKamyar Afarinkia
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Rebecca M HarmanGerlinde R Van de Walle
Jun 27, 2021·Cellular & Molecular Immunology·Yan-Hong LiMei-Rong Du
Jul 28, 2021·Expert Opinion on Drug Delivery·Yukiya TakayamaMakiya Nishikawa

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Methods Mentioned

BETA
FACS
ELISA
PCR
electrophoresis
transfection
flow cytometry

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