A Clinical Study of CAR-T Cells in the Treatment of Relapsed and Refractory Hematological Malignancies

2019 ◽  
Author(s):  
Keyword(s):  
T Cells ◽  
Clinical Study ◽  
Hematological Malignancies ◽  
Car T Cells ◽  
Car T

scholarly journals Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing-Zhou Hou ◽  
Jing Christine Ye ◽  
Jeffrey J. Pu ◽  
Hongtao Liu ◽  
Wei Ding ◽  
...  
Keyword(s):  
New York ◽  
T Cells ◽  
Annual Meeting ◽  
Hematological Malignancies ◽  
Novel Agents ◽  
Car T Cells ◽  
Car T ◽  
Bruton Tyrosine Kinase ◽  
Engineered T Cells ◽  
American Society

AbstractAntibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.

scholarly journals Chimeric Antigen Receptor T Cell Exhaustion during Treatment for Hematological Malignancies

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Chunyi Shen ◽  
Zhen Zhang ◽  
Yi Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Immunotherapy, especially based on chimeric antigen receptor (CAR) T cells, has achieved prominent success in the treatment of hematological malignancies. However, approximately 30-50% of patients will have disease relapse following remission after receiving CD19-targeting CAR-T cells, with failure of maintaining a long-term effect. Mechanisms underlying CAR-T therapy inefficiency consist of loss or modulation of target antigen and CAR-T cell poor persistence which mostly results from T cell exhaustion. The unique features and restoration strategies of exhausted T cells (Tex) have been well described in solid tumors. However, the overview associated with CAR-T cell exhaustion is relatively rare in hematological malignancies. In this review, we summarize the characteristics, cellular, and molecular mechanisms of Tex cells as well as approaches to reverse CAR-T cell exhaustion in hematological malignancies, providing novel strategies for immunotherapies.

scholarly journals Strategies to Circumvent the Side-Effects of Immunotherapy Using Allogeneic CAR-T Cells and Boost Its Efficacy: Results of Recent Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergei Smirnov ◽  
Alexey Petukhov ◽  
Ksenia Levchuk ◽  
Sergey Kulemzin ◽  
Alena Staliarova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Hematological Malignancies ◽  
Host Immune System ◽  
Extensive Area ◽  
Graft Versus Host ◽  
Car T Cells ◽  
Results Of Treatment ◽  
Car T ◽  
Life Threatening

Despite the outstanding results of treatment using autologous chimeric antigen receptor T cells (CAR-T cells) in hematological malignancies, this approach is endowed with several constraints. In particular, profound lymphopenia in some patients and the inability to manufacture products with predefined properties or set of cryopreserved batches of cells directed to different antigens in advance. Allogeneic CAR-T cells have the potential to address these issues but they can cause life-threatening graft-versus-host disease or have shorter persistence due to elimination by the host immune system. Novel strategies to create an “off the shelf” allogeneic product that would circumvent these limitations are an extensive area of research. Here we review CAR-T cell products pioneering an allogeneic approach in clinical trials.

scholarly journals CAR T-Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds against Hematological Malignancies

2018 ◽  
Author(s):  
Jonathan P Mochel ◽  
Stephen C Ekker ◽  
Chad M Johannes ◽  
Albert E Jergens ◽  
Karin Allenspach ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hematological Malignancies ◽  
B Cell Lymphoma ◽  
Car T Cells ◽  
Car T Cell ◽  
Oncology Research ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

scholarly journals The tumor vasculature an attractive CAR T cell target in solid tumors

Angiogenesis ◽  
2019 ◽  
Vol 22 (4) ◽  
pp. 473-475 ◽  
Author(s):  
Parvin Akbari ◽  
Elisabeth J. M. Huijbers ◽  
Maria Themeli ◽  
Arjan W. Griffioen ◽  
Judy R. van Beijnum
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Hematological Malignancies ◽  
Tumor Vasculature ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract T cells armed with a chimeric antigen receptor, CAR T cells, have shown extraordinary activity against certain B lymphocyte malignancies, when targeted towards the CD19 B cell surface marker. These results have led to the regulatory approval of two CAR T cell approaches. Translation of this result to the solid tumor setting has been problematic until now. A number of differences between liquid and solid tumors are likely to cause this discrepancy. The main ones of these are undoubtedly the uncomplicated availability of the target cell within the blood compartment and the abundant expression of the target molecule on the cancerous cells in the case of hematological malignancies. Targets expressed by solid tumor cells are hard to engage due to the non-adhesive and abnormal vasculature, while conditions in the tumor microenvironment can be extremely immunosuppressive. Targets in the tumor vasculature are readily reachable by CAR T cells and reside outside the immunosuppressive tumor microenvironment. It is therefore hypothesized that targeting CAR T cells towards the tumor vasculature of solid tumors may share the excellent effects of CAR T cell therapy with that against hematological malignancies. A few reports have shown promising results. Suggestions are provided for further improvement.

scholarly journals Chimeric Antigen Receptor–Modified T Cells and T Cell–Engaging Bispecific Antibodies: Different Tools for the Same Job

2021 ◽  
Author(s):  
Melanie Schwerdtfeger ◽  
Mohamed-Reda Benmebarek ◽  
Stefan Endres ◽  
Marion Subklewe ◽  
Vincenzo Desiderio ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
Major Area ◽  
Car T Cells ◽  
Car T ◽  
Target Effects

Abstract Purpose of Review Both chimeric antigen receptor (CAR) T cells and T cell–engaging antibodies (BiAb) have been approved for the treatment of hematological malignancies. However, despite targeting the same antigen, they represent very different classes of therapeutics, each with its distinct advantages and drawbacks. In this review, we compare BiAb and CAR T cells with regard to their mechanism of action, manufacturing, and clinical application. In addition, we present novel strategies to overcome limitations of either approach and to combine the best of both worlds. Recent Findings By now there are multiple approaches combining the advantages of BiAb and CAR T cells. A major area of research is the application of both formats for solid tumor entities. This includes improving the infiltration of T cells into the tumor, counteracting immunosuppression in the tumor microenvironment, targeting antigen heterogeneity, and limiting off-tumor on-target effects. Summary BiAb come with the major advantage of being an off-the-shelf product and are more controllable because of their half-life. They have also been reported to induce less frequent and less severe adverse events. CAR T cells in turn demonstrate superior response rates, have the potential for long-term persistence, and can be additionally genetically modified to overcome some of their limitations, e.g., to make them more controllable.

scholarly journals CAR T-Cell Therapy in Hematological Malignancies

2021 ◽  
Vol 22 (16) ◽  
pp. 8996
Author(s):  
Theresa Haslauer ◽  
Richard Greil ◽  
Nadja Zaborsky ◽  
Roland Geisberger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hematological Malignancies ◽  
Lymphocytic Leukemia ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T Cell ◽  
Promising Therapeutic Approach ◽  
Car T

Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.

scholarly journals Cytomorphology of Chimeric Antigen Receptor T-Cells (CAR-T)

2021 ◽  
Vol 13 (1) ◽  
pp. e2021066
Author(s):  
Eugenio Galli ◽  
Silvia Bellesi ◽  
Marcello Viscovo ◽  
Federica Sorà ◽  
Stefan Hohaus ◽  
...  
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Cell Lymphoma ◽  
Antigen Receptor ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Lymphoid Cells ◽  
Car T Cells ◽  
Car T

Chimeric antigen receptor (CAR) T cells represent one of the newest frontiers of cell therapy. Their application currently involves relapsed/refractory aggressive B cell lymphoma and leukemia as a standard of care, while several studies are exploring CAR-T to treat multiple myeloma and other hematological malignancies. Here we describe the cytomorphology of CAR-T collected from the leftovers of infusion bags, and therefore before the encounter with the antigen, with, among others, a peculiar population of giant lymphoid cells with blastoid features and hypertrophic centrosome.

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