SOHO State of the Art Updates and Next Questions: T-Cell-Directed Immune Therapies for Multiple Myeloma: Chimeric Antigen Receptor-Modified T Cells and Bispecific T-Cell-Engaging Agents.

SOHO State of the Art Updates and Next Questions: T-Cell-Directed Immune Therapies for Multiple Myeloma: Chimeric Antigen Receptor-Modified T Cells and Bispecific T-Cell-Engaging Agents. Clin Lymphoma Myeloma Leuk. 2019 Aug 07;: Authors: Madduri D, Dhodapkar MV, Lonial S, Jagannath S, Cho HJ Abstract Therapeutic monoclonal antibodies targeting SLAMF7 and CD38 are the first classes of targeted immunotherapies approved for multiple myeloma, a cancer of plasma cells. These agents are effective, particularly in combination with the immunomodulatory drugs lenalidomide and pomalidomide. The next generation of myeloma immunotherapy under investigation consists of T-cell-directed strategies designed to promote cytotoxic activity against myeloma cells, as embodied by chimeric antigen receptor-modified T cells (CAR-T) and bispecific T-cell-engaging agents. Early clinical trial results with these classes of therapies are promising, with high response rates reported. These strategies appear to be strong activators of immunoresponse, and adverse effects, particularly cytokine release syndrome and cytokine-related encephalopathic syndrome, are common. Ongoing research explores the optimal disease setting and combination therapies for these agents. These studies provide an unprecedented opportunity to understand the mechanisms of action and their relations to adverse effects and resistance to therapy. PMID: 31427259 [PubMed - as supplied by publisher]
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Lymphoma Myeloma Leuk Source Type: research

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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
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
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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
Cancer immunotherapies have primarily focused on generating tumoricidal CD8 T cells. However, recent data demonstrate a critical role for CD4 T cells in tumor immunity. CD4 T cells against epitopes derived from mutated tumor-associated neo-antigens (neoAg) conferred protection against tumor growth in animal models of neoAg vaccine therapy. In clinical studies, immunity elicited by neoAg vaccines was associated with improved survival, even though the majority of immune responses were CD4 T cells that did not have cytolytic activity.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Despite the compelling clinical success of chimeric antigen receptor (CAR)-T cells and bispecific T cell engagers (BiTEs) for the treatment of multiple myeloma (MM), many patients relapse due to tumor escape. A list of limitations exists for both immunotherapies. CAR-T cells, for instance, 1) only target one cancer antigen when it is evidently known that cancer cells express a landscape of heterotypic genes and moieties; and 2) are extremely expensive with a total cost of more than $1 million. With regards to BiTEs, limitations arise from: 1) the inability to target multiple cancer antigens; 2) the need to be continually i...
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Immunotherapeutic Approaches to Multiple Myeloma Source Type: research
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Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5 –10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective managemen...
Source: Frontiers of Medicine - Category: General Medicine Source Type: research
AbstractIt is well recognized that CD4+ T cells may play an important role in immunosurveillance and immunotherapy against cancer. However, the details of how these cells recognize and eliminate the tumor cells remain incompletely understood. For the past 25  years, we have focused on how CD4+ T cells reject multiple myeloma cells in a murine model (MOPC315). In our experimental system, the secreted tumor-specific antigen is taken up by tumor-infiltrating macrophages that process it and present a neoepitope [a V region-derived idiotypic (Id) peptide] on MHC class II molecules to Th1 cells. Stimulated Th1 cells produce...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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