Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and CD25-targeted antibody for transplanted Lewis lung carcinoma cells

Journal of Immunotherapy
Cheol-Hun SonYou-Soo Park

Abstract

Regulatory T cells (Tregs) is one of the main obstacles to the success of cancer immunotherapy. The effect of dendritic cell (DC)-based immunotherapy can be attenuated by immune suppressive functions of Tregs. We used a CD25-targeted antibody and low-dose cyclophosphamide (CTX) as immunomodulators to increase the antitumor effect of intratumoral injection of immature DCs into the irradiated tumor cells (IR/iDC). CTX or CD25-targeted antibody alone showed a significant reduction in the number of Tregs within the tumor microenvironment. When they are combined with IR/iDC, the number of Tregs was further reduced. Although IR/IDC showed strong antitumor effects such as reduction in tumor growth, increase in Th1 immune response, and improvement of survival, the therapeutic effect was further improved by combining treatments with immunomodulators. CTX and CD25-targeted antibody showed no significant difference in tumor growth when combined with IR/iDC, but CTX further increased the number of interferon (IFN)-γ-secreting T cells, cytotoxicity, and survival rate. Although irradiation induced depletion of T lymphocytes, administration of DCs recovered this depletion. Particularly, the lymphocytes were more significantly increased when C...Continue Reading

References

Apr 5, 2001·Trends in Immunology·M LarssonN Bhardwaj
Aug 13, 2002·Current Pharmaceutical Design·Eric J Friedman
Jan 21, 2006·Seminars in Cancer Biology·Rong-Fu Wang
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Jul 4, 2009·The Lancet Oncology·Silvia C Formenti, Sandra Demaria

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Citations

Mar 11, 2015·International Journal of Radiation Oncology, Biology, Physics·Cheol-Hun SonYou-Soo Park
Feb 21, 2018·Immunology·Ellyn HughesAwen Gallimore
Jun 22, 2019·Journal of Cellular Physiology·Monireh MohsenzadeganRaheleh Roudi
May 22, 2021·Translational Oncology·Zhuo ChenJingbo Wu

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Methods Mentioned

BETA
biopsy
Assay
flow cytometry

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