POTENT ANTI-MYELOMA EFFICACY OF DENDRITIC CELL THERAPY IN COMBINATION WITH POMALIDOMIDE AND PROGRAMMED DEATH-LIGAND 1 BLOCKADE IN A PRECLINICAL MODEL OF MULTIPLE MYELOMA
Author(s): ,
Sung-Hoon Jung
Affiliations:
Department of Hematology-Oncology,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Tan-Huy Chu
Affiliations:
Research Center for Cancer Immunotherapy,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Manh-Cuong Vo
Affiliations:
Research Center for Cancer Immunotherapy,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Hye-Seong Park
Affiliations:
Research Center for Cancer Immunotherapy,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Thangaraj Jaya Lakshmi
Affiliations:
Research Center for Cancer Immunotherapy,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Seo-Yeon Ahn
Affiliations:
Department of Hematology-Oncology,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
,
Hyeoung-Joon Kim
Affiliations:
Department of Hematology-Oncology,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
Je-Jung Lee
Affiliations:
Department of Hematology-Oncology,CHONNAM NATIONAL UNIVERSITY HWASUN HOSPITAL,Hwasun-Eup,Korea, Republic Of
EHA Library. Lee J. Jun 15, 2019; 266975; PS1358
Je-Jung Lee
Je-Jung Lee
Contributions
Abstract

Abstract: PS1358

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background

Dendritic cell (DC)-based vaccines are recognized as a promising immunotherapeutic strategy against cancer, and various combination approaches have been developed to enhance DC function by modulating immune responses and tumor microenvironment.

Aims

In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand-1 (PD-L1) blockade in a murine model of multiple myeloma (MM).

Methods

MOPC-315 cell lines were injected subcutaneously to establish MM bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs + pomalidomide/dexamethasone, (3) Pomalidomide/dexamethasone + PD-L1 blockade, and (4) DCs + pomalidomide/dexamethasone + PD-L1 blockade.

Results

The combination of DCs + pomalidomide with dexamethasone + PD-L1 blockade inhibited more strongly tumor growth and prolonged survival of treated mice compared to the other groups. This effect was associated with a significant reduction in immune suppressor cells, such as myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages, and level of immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor-β, and interleukin-10, and with the significant induction of immune effector cells, such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, in the spleen and tumor microenvironment. Functional activities of cytotoxic T lymphocytes and NK cells in spleen were also enhanced by the combination of DCs + pomalidomide with dexamethasone + PD-L1 blockade.

Conclusion

The collective findings in the murine MM model suggest that DC vaccination combined with pomalidomide and PD-L1 blockade synergistically enhance antitumor immunity through two-way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research

Keyword(s): Dendritic cell, Immunotherapy, Multiple myeloma

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