Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens

Vidal-Crespo, Anna; Matas-Céspedes, Alba; Rodríguez, Vanina; Rossi, Cédric; Valero, Juan García; Serrat, Neus; Sanjuán-Pla, Alejandra; Menéndez, Pablo; Roué, Gaël; López‐Guillermo, Armando; Giné, Eva; Campo, Elı́as; Colomer, Dolors; Bezombes, Christine; Bueren, Jeroen Lammerts van; Chiu, Christopher; Doshi, Parul; Pérez-Galán, Patricia

doi:10.3324/haematol.2018.211904

Cited by 34 publications

(23 citation statements)

References 44 publications

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“…S4B). At the endpoint, the control liposome group showed systemic disease, with spleen, brain, and BM infiltration in agreement with previous results [35]. Mice treated with clodronate liposomes showed a significant reduction of tumor load and dissemination to BM and brain as quantified by bioluminescence ( Fig.…”

Section: Macrophage Depletion Hampers the Outgrowth Of Fl-hk Tumors Asupporting

confidence: 91%

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

et al. 2021

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Microenvironment contributes to follicular lymphoma (FL) pathogenesis and impacts survival with macrophages playing a controversial role. In the present study, using FL primary samples and HK follicular dendritic cells (FDC) to mimic the germinal center, together with mouse models, we have analyzed the three-way crosstalk of FL-FDC-macrophages and derived therapeutic opportunities. Ex vivo primary FL-FDC co-cultures (n = 19) and in vivo mouse co-xenografts demonstrated that FL-FDC crosstalk favors tumor growth and, via the secretion of CCL2 and CSF-1, promotes monocyte recruitment, differentiation, and polarization towards an M2-like protumoral phenotype. Moreover, FL-M2 co-cultures displayed enhanced angiogenesis, dissemination, and immunosuppression. Analysis of the CSF-1/CSF-1R pathway uncovered that CSF-1 was significantly higher in serum from grade 3A FL patients, and that high CSF-1R expression in FL biopsies correlated with grade 3A, reduced overall survival and risk of transformation. Furthermore, CSF-1R inhibition with pexidartinib (PLX3397) preferentially affected M2-macrophage viability and polarization program disrupting FL-M2 positive crosstalk. In vivo CSF1-R inhibition caused M2 reduction and repolarization towards M1 macrophages and antitumor effect cooperating with anti-CD20 rituximab. In summary, these results support the role of macrophages in FL pathogenesis and indicate that CSF-1R may be a relevant prognostic factor and a novel therapeutic target cooperating with anti-CD20 immunotherapy.

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Section: Macrophage Depletion Hampers the Outgrowth Of Fl-hk Tumors Asupporting

confidence: 91%

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

et al. 2021

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“…Evidence of Daratumumab-mediated ADCC and ADCP was also demonstrated in in vitro and in vivo models of NHL (MCL, FL and DLBCL), independently of CD38 expression levels [87]. However, a phase II study assessing the activity of Daratumumab monotherapy in relapsed/refractory NHL failed to produce significant results, with only 8% of patients achieving a response (12.5% of FL and 6.7% of DLBCL) [69].…”

Section: Therapeutic Implications: Daratumumab As Monotherapy or Combmentioning

confidence: 96%

“…Although monotherapy with Daratumumab does not exhibit effective cytotoxic activity, combination therapy with standard regimens may enhance response rates. Indeed, Vidal-Crespo et al have also shown that Daratumumab potentiates the effects of R-CHOP activity in preclinical models of FL, MCL and DLBCL [87]. Clinical studies are thus warranted to assess the benefit of this combination in patients affected by NHL.…”

Section: Therapeutic Implications: Daratumumab As Monotherapy or Combmentioning

confidence: 99%

The Many Facets of CD38 in Lymphoma: From Tumor–Microenvironment Cell Interactions to Acquired Resistance to Immunotherapy

Calabretta¹,

Carlo‐Stella

2020

Cells

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The CD38 antigen is expressed in several hematological malignancies, and the anti-CD38 monoclonal antibodies Daratumumab and Isatuximab have an established role in the therapy of multiple myeloma. However, data on the therapeutic utility of CD38 targeting in other lymphoid malignancies are limited. In chronic lymphocytic leukemia, the prognostic significance of CD38 expression is well accepted, and preclinical studies on the use of Daratumumab in monotherapy or combination therapy have demonstrated considerable efficacy. In other lymphoproliferative disorders, preclinical and clinical data have not been as compelling; however, CD38 overexpression likely contributes to resistance to checkpoint inhibitors, prompting numerous clinical trials in Hodgkin and non-Hodgkin lymphoma to investigate whether blocking CD38 enhances the efficacy of checkpoint inhibitors. Furthermore, due to its widespread expression in hematological tumors, CD38 represents an attractive target for cellular therapies such as CAR-T cells. The present review discusses current knowledge of CD38 expression and its implications in various lymphoid malignancies. Furthermore, it addresses current and future therapeutic perspectives, with a particular emphasis on the significance of CD38 interaction with immune cells of the tumor microenvironment. Lastly, results of ongoing studies using anti-CD38 antibodies will be reviewed.

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“…Moreover, surprisingly daratumumab shown FC mediated cytotoxicity, ADCC, CDC and ADCP activity in all subtype of lymphomas. As compared with rituximab, daratumumab showed better results in vivo mouse model based follicular lymphoma therapies [55].…”

Section: Monoclonal Antibody For Lymphoma Treatmentmentioning

confidence: 99%

Development of Therapeutic Antibody Technology And Recent Perspectives For Leukemia-Lymphoma Treatment

Yirga¹,

Lin²,

Huang³

et al. 2019

J Leuk

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Advancement of monoclonal antibodies (Mabs) to be accepted as a therapy has long history. This article describes the dramatic developmental trend of therapeutic antibody technology and their significant role for treatment of leukemia-lymphoma at the current time. The therapeutic Mab technology development from murine (mouse origin) to fully human resulted in low immunogenicity and high quality Mabs. Chemotherapy is standard care for leukemialymphoma treatments. However, it is associated with high toxicities (side effects), painful and relatively ineffective against certain leukemia-lymphoma subtypes. The remarkable contribution of Von Behring, Paul Ehrlich and the discovery of hybridoma technology marked the beginning of antibodies for therapeutic applications. Rituximab is the first Mab approved by Food and Drug Administration against B-cell malignancies. Today, a number of effective Mabs targeting leukemia and lymphoma were approved and successfully developed. The Mab therapeutic phenomena in the body (also called war in the blood) has various mechanism of actions. In recent years, Mab against leukemialymphoma achieved significantly therapeutic outcomes, eventually this led to traditional chemotherapy treatment free era. We also reviewed that, the therapeutic efficacy of Mabs against leukemia-lymphoma as compared antibody alone and antibody conjugated with potent chemotherapy or cytotoxic drugs. This article extends our understanding of advancements in therapeutic Mabs technology and provides new insights of Mab leukemia-lymphomas therapy. We also encourage further more studies for Mab based diagnostics, treatments of leukemia and lymphomas.

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Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens

Cited by 34 publications

References 44 publications

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma

The Many Facets of CD38 in Lymphoma: From Tumor–Microenvironment Cell Interactions to Acquired Resistance to Immunotherapy

Development of Therapeutic Antibody Technology And Recent Perspectives For Leukemia-Lymphoma Treatment

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