Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells

ConclusionsOur results demonstrate that in vitro activation affects NK cell anti-myeloma activity in vivo by regulating their BM infiltration. Furthermore, we provided direct evidence that CXCR3 restrains NK cell anti-tumor capacity in vivo according to the activation protocol used, and that the effects of NK cell-based adoptive immunotherapy for multiple myeloma can be improved by increasing their bone marrow homing through CXCR3 inhibition.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research

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Chimeric antigen receptor (CAR)-T cell therapy is a new and powerful class of cancer immunotherapy [1,2]. Clinical trials of CAR-T cell therapy targeting the B-cell marker CD19 have shown promising results for the treatment of hematologic malignancies, including acute lymphoblastic leukemia (ALL) [3 –7], chronic lymphocytic leukemia (CLL) [8,9], and non-Hodgkin lymphoma (NHL) [10,11]. CAR-T cell therapy targeting B-cell maturation antigen (BCMA) has also been demonstrated to be effective for treating multiple myeloma (MM) [12–15].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
ConclusionsThese data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
The initial findings from a small clinical trial of patients with multiple myeloma or sarcoma suggest that gene-edited immunotherapy is safe.
Source: The Scientist - Category: Science Tags: News & Opinion Source Type: news
We describe three clinical scenarios in which CAR T- cell immunotherapy interfered with HIV-1 testing including: (1) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B-cell acute lymphoblastic leukemia, status post CAR T- cell treatment (2) routine infectious disease screening prior to 2nd CAR T- cell collection in a 65-year-old male with diffuse large B-cell lymphoma who failed initial CAR T- cell treatment and (3) routine infectious risk assessment following an occupational health exposure from a 58 -year-old male with multiple myeloma, status post CAR T- cell treatment...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Clin Microbiol Source Type: research
ConclusionThis study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Non-genetic cellular plasticity has recently emerged as a basis for therapeutic resistance in cancer. Therefore, a better understanding of cellular plasticity and adaptive state changes in myeloma cells and the immune microenvironment is critical to develop effective therapeutic approaches that can overcome drug resistance. We performed fluorescence activated cell sorting and full-length single-cell RNA sequencing of myeloma cells and CD45+ immune cells from the bone marrow of 8 patients with relapsed/refractory multiple myeloma (RRMM) treated on a clinical trial with elotuzumab, pomalidomide, bortezomib and dexamethasone ...
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
In some patients with multiple myeloma (MM), the original M protein disappears and one or multiple smaller immunoglobulins, called oligoclonal bands (OCB), emerge following autologous stem cell transplant (ASCT). OCB are associated with improved disease-free survival (DFS) and may be associated with early immune system recovery. Patients in phase I/II clinical trials at the University of Maryland Greenebaum Cancer Center who received anti CD3-CD28 co-stimulated and engineered autologous T cells shortly after ASCT had early, rapid, and robust T cell recovery.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Immunotherapy has achieved unprecedent long-term survival rates in solid tumors and has begun to transform myeloma (MM) treatment as well. Among strategies to enhance cancer cell immunogenicity, induction of immunogenic cell death (ICD) is particularly promising: the release of danger signals from dying cancer cells may, indeed, stimulate a specific anti-cancer immunity via T-cell priming by dendritic cells (DCs). Here, we sought to investigate the molecular basis and clinical relevance of bortezomib (BTZ)-induced ICD in MM.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
T cell-engaging immunotherapies are changing the therapeutic landscape of cancer. However, suitable target antigens are scarce, restricting these strategies to very few tumor types. To overcome this limitation, we developed a T cell-engaging antibody derivative, which comes in two complementary halves and addresses antigen combinations instead of single molecules. Each half, originally coined hemibody, contains an antigen specific single-chain variable fragment fused to either the variable light (VL) or variable heavy (VH) chain domain of an anti-CD3 antibody.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
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