BCMA-Targeted Immunotherapy Can Lead to Durable Responses In Multiple Myeloma

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Source: Oncology Times - Category: Cancer & Oncology Tags: News Source Type: research

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(Huntsman Cancer Institute) In research published today in the journal Nature Communications, Utah-based scientists describe a novel way to treat cancers using chimeric antigen receptor (CAR) T cell therapy. Laboratory tests using mouse models and tumor cells from patients displayed promising results for this novel cellular immunotherapy for multiple myeloma and other types of blood cancer.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Authors: Yu M, Ye J, Cao S, Liu X, Chen Z Abstract The DNA fragment encoding predicted main antigenic region, aa 1-300 on Gp protein of Ebola virus (EBOV) was cloned into the vector pGEX-KG. The recombinant GST-tagged Gp-300 was expressed in Escherichia coli BL21 (DE3) by induction with 1 mM isopropyl-1-thio-b-d-galactoside and purified by dialysis. Four monoclonal antibodies (mAbs) named 1C4, 2A3, 2G7, and 2H9 against Gp protein were generated by fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from Gp-300 protein-immunized mice. The activity of the mAbs was then characterized by enzyme-linked i...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research
The transferrin receptor 1 (TfR1) is a meaningful target for antibody-based cancer therapy given its overexpression on malignant cells and its central role in cancer pathology. We previously developed a mouse/human chimeric IgG3 targeting human TfR1 (ch128.1), which exhibits significant antitumor activity against multiple myeloma (MM) in xenograft models of SCID-Beige mice bearing disseminated ARH-77 or KMS-11 tumors. This activity is observed in early and late disease stages of disseminated KMS-11 tumors and, in this model, the mechanism of antitumor activity is Fc-mediated, involving macrophages. As human IgG1 is the iso...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
ConclusionsOur results demonstrate that the incidence of GVHD after daratumumab is low and did not result in increased exacerbation of GVHD in patients with prior history of GVHD.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1+ or NKG2D+ GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we hypothesized that blocking the “don’t eat me” signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations in the bone marrow. These findings indicate that CD47 is specifically expressed on MM and can be used as a potential therapeutic target. Further, blocking of CD47 using an anti-CD47 antibody induced immediate activation of macrophages, which resulted in induct...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Chimeric antigen receptor (CAR) T cell therapy, an immunotherapy using gene-modified T cells, has recently made a big success. CAR T cells targeting CD19 is highly effective against B cell malignancies. Next good target for CAR T therapy is multiple myeloma. B cell maturation antigen has been proved to be a good target for CAR T cell therapy in early-phase clinical trials. We are also developing CAR T cells targeting a protein conformation that is preferentially detected in myeloma cells. In this review, I will summarize the state of art in the field of CAR T cell therapy against myeloma, and also present...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
Cellular immunotherapy is a rapidly progressing field in multiple myeloma (MM). Multiple clinical trials have reported impressive efficacy of B cell maturation antigen (BCMA) directed chimeric antigen receptor cell therapy (BCMA CART) in MM. While trials demonstrated a high response rate, the durable response rate is around 30%. Most patients lose their CART cells, and the disease relapses within the first year, suggesting an inhibition by the MM tumor microenvironment (TME). Therefore strategies to overcome this inhibition would represent a major advance in this field.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 333 Source Type: research
Publication date: Available online 13 January 2020Source: Best Practice &Research Clinical HaematologyAuthor(s): Urvi A. Shah, Sham MailankodyAbstractMultiple myeloma (MM) is a haematologic malignancy with significant improvements in the overall survival over the last decade. However, patients still relapse and die due to a lack of treatment options. Ultimately, novel therapies with the potential for long term remissions are needed for patients with advanced MM. Research efforts for such immune therapies were not successful until recently when the first immunotherapies for MM were approved in 2015 and many more are und...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
AbstractMultiple myeloma (MM) is a clonal plasma cell malignancy typically associated with the high and uniform expression of the CD38 transmembrane glycoprotein. Daratumumab is a humanized IgG1 κ CD38 monoclonal antibody (MoAb) which has demonstrated impressive single agent activity even in relapsed refractory MM patients as well as strong synergy with other anti-MM drugs. Natural Killer (NK) cells are cytotoxic immune effector cells that mediate in vivo tumour immunosurveillance. NK cell s also play an important role during MoAb therapy by inducing antibody dependent cellular cytotoxicity (ADCC) via their Fcγ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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