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

Chu, Tan-Huy; Vo, Manh-Cuong; Park, Hye-Seong; Lakshmi, Thangaraj Jaya; Jung, Sung‐Hoon; Kim, Hyeoung-Joon; Lee, Je‐Jung

doi:10.1007/s00262-020-02654-0

Cited by 21 publications

(7 citation statements)

References 46 publications

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“…Similar results were obtained when combining dying MM cell-loaded DC therapy with pomalidomide and dexamethasone [154]. The most promising prognosis in a preclinical MM model was obtained after quadruple combination therapy, including dying MM cell-loaded DC therapy, pomalidomide, dexamethasone, and anti-PD-1 therapy [155]. In this regard, a phase II clinical trial is currently being performed, examining the therapeutic potential of combining lenalidomide and DC/MM fusion vaccination in MM patients previously subjected to auto-HSCT (clinicaltrials.gov identifier: NCT02728102) (Table 2).…”

Section: Combination Strategies To Enhance the Efficacy Of Dc-based Immunotherapy In MMsupporting

confidence: 67%

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges, Opportunities, and Future Directions

Verheye

Melgar

Deschoemaeker

et al. 2022

IJMS

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Immunotherapeutic approaches, including adoptive cell therapy, revolutionized treatment in multiple myeloma (MM). As dendritic cells (DCs) are professional antigen-presenting cells and key initiators of tumor-specific immune responses, DC-based immunotherapy represents an attractive therapeutic approach in cancer. The past years, various DC-based approaches, using particularly ex-vivo-generated monocyte-derived DCs, have been tested in preclinical and clinical MM studies. However, long-term and durable responses in MM patients were limited, potentially attributed to the source of monocyte-derived DCs and the immunosuppressive bone marrow microenvironment. In this review, we briefly summarize the DC development in the bone marrow niche and the phenotypical and functional characteristics of the major DC subsets. We address the known DC deficiencies in MM and give an overview of the DC-based vaccination protocols that were tested in MM patients. Lastly, we also provide strategies to improve the efficacy of DC vaccines using new, improved DC-based approaches and combination therapies for MM patients.

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Section: Combination Strategies To Enhance the Efficacy Of Dc-based Immunotherapy In MMsupporting

confidence: 67%

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges, Opportunities, and Future Directions

Verheye

Melgar

Deschoemaeker

et al. 2022

IJMS

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“…PD1 expression on NK cells has been demonstrated as well in other tumor entities like Kaposi sarcoma (110), digestive cancers (111) and multiple myeloma (112). Using GM-CSF/IL-4 bone marrow-derived DCs (BMDCs) for vaccination in combination with pomalidomide and PD-L1 blockade, a significant tumor growth inhibition within a multiple myeloma mouse model could be achieved (113). Similar results were reported when using vaccination with GM-CSF/IL-4-derived BMDCs together with lenalidomide and PD1 blockade, which resulted in an increased functional activity of T and NK cells as well as a reduction of immunosuppressive cytokines within the TME (114).…”

Section: Blockade Of Immune Checkpoint (Icp) Receptorsmentioning

confidence: 99%

Characterization and Manipulation of the Crosstalk Between Dendritic and Natural Killer Cells Within the Tumor Microenvironment

et al. 2021

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Cellular therapy has entered the daily clinical life with the approval of CAR T cell therapeutics and dendritic cell (DCs) vaccines in the US and the EU. In addition, numerous other adoptive cellular products, including natural killer (NK) cells, are currently evaluated in early phase I/ II clinical trials for the treatment of cancer patients. Despite these promising accomplishments, various challenges remain to be mastered in order to ensure sustained therapeutic success. These include the identification of strategies by which tumor cells escape the immune system or establish an immunosuppressive tumor microenvironment (TME). As part of the innate immune system, DCs and NK cells are both present within the TME of various tumor entities. While NK cells are well known for their intrinsic anti-tumor activity by their cytotoxicity capacities and the secretion of pro-inflammatory cytokines, the role of DCs within the TME is a double-edged sword as different DC subsets have been described with either tumor-promoting or -inhibiting characteristics. In this review, we will discuss recent findings on the interaction of DCs and NK cells under physiological conditions and within the TME. One focus is the crosstalk of various DC subsets with NK cells and their impact on the progression or inhibition of tumor growth. In addition, we will provide suggestions to overcome the immunosuppressive outcome of the interaction of DCs and NK cells within the TME.

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“…Nevertheless, tumor cells often protect themselves from the host immune system by inhibiting the anti-tumor immunity of their surrounding microenvironment. The sophisticated interplays between immune microenvironment and this disease may affect the clinical responses to immuno-oncology therapies such as thalidomide, lenalidomide ( 14 ) as well as pomalidomide ( 15 ). Early studies have mainly established the role of the bone marrow microenvironment in the pathological process of multiple myeloma, but the immune components of the microenvironment have not received enough attention.…”

Section: Introductionmentioning

confidence: 99%

FABP5, a Novel Immune-Related mRNA Prognostic Marker and a Target of Immunotherapy for Multiple Myeloma

et al. 2021

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Objective: Multiple myeloma is an incurable hematological malignancy. It is imperative to identify immune markers for early diagnosis and therapy. Here, this study analyzed immune-related mRNAs and assessed their prognostic value and therapeutic potential.Methods: Abnormally expressed immune-related mRNAs were screened between multiple myeloma and normal bone marrow specimens in the GSE47552 and GSE6477 datasets. Their biological functions were then explored. Survival analysis was presented for assessing prognosis-related mRNAs. CIBERSORT was utilized for identifying 22 immune cell compositions of each bone marrow specimen. Correlation between FABP5 mRNA and immune cells was then analyzed in multiple myeloma.Results: Thirty-one immune-related mRNAs were abnormally expressed in multiple myeloma, which were primarily enriched in B cells-related biological processes and pathways. Following validation, FABP5 mRNA was a key risk factor of multiple myeloma. Patients with its up-regulation usually experienced unfavorable outcomes. There were distinct differences in the infiltration levels of B cells naïve, B cells memory, plasma cells, T cells CD4 naïve, resting memory CD4 T cells, activated memory CD4 T cells, Tregs, resting NK cells, M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils between multiple myeloma and normal samples. FABP5 mRNA had correlations to B cells memory, B cells naïve, dendritic cells activated, macrophages M0, macrophages M1, macrophages M2, neutrophils, activated NK cells, resting memory CD4 T cells, CD8 T cells and Tregs.Conclusion: Collectively, our data showed that FABP5 mRNA was related to immune microenvironment, which could be a target of immunotherapy and prognostic marker for multiple myeloma.

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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

Cited by 21 publications

References 46 publications

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges, Opportunities, and Future Directions

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges, Opportunities, and Future Directions

Characterization and Manipulation of the Crosstalk Between Dendritic and Natural Killer Cells Within the Tumor Microenvironment

FABP5, a Novel Immune-Related mRNA Prognostic Marker and a Target of Immunotherapy for Multiple Myeloma

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