Molecular dynamics of targeting CD38 in multiple myeloma
نویسندگان
چکیده
Multiple functions of CD38 need exploring to expand clinical application anti-CD38 antibodies in multiple myeloma (MM). We investigated membrane dynamics MM cells and subsequent events when is targeted by therapeutic antibodies. Human (BF01) were co-cultured vitro with antibody (or control immunoglobulin G) analysed using gene expression profiling. Microvesicles from antibody-exposed for differential microRNA (miRNA) expression, phenotypic characterisation. Exposure BF01 resulted redistribution, upregulation metabolism-related genes downregulation involved cell cycle processes. derived showed increased CD73 CD39 presence programmed death-ligand 1 significant up-/down-modulation miRNAs. accumulated around Fc receptor-positive (FcR+) cells. Upon internalisation, natural killer displayed significantly related activation immune response, the cycle. Cells may use microvesicles transmit signals distally as part a survival strategy. are equipped on their surface enzymatic machinery leading production tolerogenic adenosine. Further, they internalised FcR+ functional modifications. These observations have relevance improving through targeting this mechanism its sequelae.
منابع مشابه
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
BACKGROUND Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of ...
متن کاملClinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma.
Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic effi...
متن کاملTargeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma.
Purpose: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ regulatory T cells (Treg) and further define immunomodulating effects of a therapeutic CD38 mAb isatuximab/SAR650984 in multiple myeloma.Experimental Design: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and multiple myeloma patients. Peripheral blood mononuclear cells (PBMC) were then treate...
متن کاملEvaluation of CD38 as Target for Immunotherapy in Multiple Myeloma
We have read with interest the report of Goldmacher et al.’ They describe the construction of an anti-CD38 imunotoxin (IT) by conjugating CD38 monoclonal antibody (MoAb) HB7 to blocked ricin. The resulting IT shows potent killing of plasma cell lines, whereas only low toxicity is observed for hematopoietic precursor cells (HPC). Therefore, they conclude that this HB7-blocked ricin may have clin...
متن کاملEvaluation of CD38 as target for immunotherapy in multiple myeloma.
We have read with interest the report of Goldmacher et al.’ They describe the construction of an anti-CD38 imunotoxin (IT) by conjugating CD38 monoclonal antibody (MoAb) HB7 to blocked ricin. The resulting IT shows potent killing of plasma cell lines, whereas only low toxicity is observed for hematopoietic precursor cells (HPC). Therefore, they conclude that this HB7-blocked ricin may have clin...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: British Journal of Haematology
سال: 2021
ISSN: ['0007-1048', '1365-2141']
DOI: https://doi.org/10.1111/bjh.17329