Chimeric Antigen Receptor T-cell Therapy for Multiple Myeloma

Relapsed/Refractory multiple myeloma remains a significant clinical challenge despite a wide array of approved therapeutic agents. Immunotherapy offers an advantage in this setting. Chimeric antigen receptor (CAR) modified T-cells have transformed care for patients with hematological malignancies. CAR-T cells targeting CD-19 B-cell lymphoma cells have shown prominent activity in lymphoma and acute lymphoblastic leukemia (ALL). Recently, the CAR-T cell platform for MM demonstrated therapeutic benefit.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Article Source Type: research

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era J Abstract The decision to incorporate allogeneic hematopoietic stem cell transplant (allo-HSCT) into front-line therapy in adult acute lymphoblastic leukemia (ALL) should be primarily guided by measurable residual disease (MRD) status and the ALL regimen utilized. While there is no doubt that allo-HSCT benefits patients with poor MRD response after induction or consolidation, the indication of allo-HSCT in cases of good MRD clearance is not clear. As targeted immunotherapies result in high MRD-negative CR rates, early incorporation of these therapies may also prove valuable in reducing the need for HCT in the...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Lymphoma Myeloma Leuk Source Type: research
Despite high complete remission (CR) rates, relapse remains a significant problem among subsets of patients with B acute lymphoblastic leukemia (ALL), and is associated with poor prognosis. The recent Food and Drug Administration approval of highly effective immunotherapies for B-lineage ALL, blinatumomab, inotuzumab ozogamicin, and tisagenlecleucel, a chimeric antigen receptor (CAR) modified T cell therapy, targeting CD19, or CD22, have dramatically changed the therapeutic landscape for the treatment of B-ALL, resulting in high rates of deep and durable remissions.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Article Source Type: research
Chimeric antigen receptor (CAR) T cell immunotherapy has been a major advancement in cancer therapeutics. Reprogramming of T cells is achieved by using gammaretroviral or lentiviral vectors, which may interfere with human immunodeficiency virus type 1 (HIV-1) nucleic acid amplification testing (NAAT). Here, we describe three clinical scenarios in which CAR T cell immunotherapy interfered with HIV-1 testing, including (i) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B cell acute lymphoblastic leukemia, post CAR T cell treatment; (ii) routine infectious disease screenin...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Virology Source Type: research
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 [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
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
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
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors. Introduction Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBC...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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