scholarly journals A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper

2022 ◽  
Author(s):  
N. Zozaya ◽  
J. Villaseca ◽  
F. Abdalla ◽  
M. A. Calleja ◽  
J. L. Díez-Martín ◽  
...  
Keyword(s):  
Care Pathway ◽  
National Health System ◽  
Think Tank ◽  
Hematological Cancer ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell Therapy ◽  
Spanish National Health System ◽  
Advanced Therapies ◽  
Car T

AbstractCAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

scholarly journals Potential strategies against resistance to CAR T-cell therapy in haematological malignancies

2020 ◽  
Vol 12 ◽  
pp. 175883592096296
Author(s):  
Qing Cai ◽  
Mingzhi Zhang ◽  
Zhaoming Li
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Haematological Malignancies ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor (CAR) T-cell therapy is a rapidly developing method for adoptive immunotherapy of tumours in recent years. CAR T-cell therapies have demonstrated unprecedented efficacy in the treatment of patients with haematological malignancies. A 90% complete response (CR) rate has been reported in patients with advanced relapse or refractory acute lymphoblastic leukaemia, while >50% CR rates have been reported in cases of chronic lymphocytic leukaemia and partial B-cell lymphoma. Despite the high CR rates, a subset of the patients with complete remission still relapse. The mechanism of development of resistance is not clearly understood. Some patients have been reported to demonstrate antigen-positive relapse, whereas others show antigen-negative relapses. Patients who relapse following CAR T-cell therapy, have very poor prognosis and novel approaches to overcome resistance are required urgently. Herein, we have reviewed current literature and research that have investigated the strategies to overcome resistance to CAR T-cell therapy.

scholarly journals Horses for Courses in the Era of CARs: Advancing CAR T and CAR NK Cell Therapies

2021 ◽  
Vol 11 (11) ◽  
pp. 1182
Author(s):  
Sergey Kulemzin ◽  
Igor Evsyukov ◽  
Tatiana Belovezhets ◽  
Alexander Taranin ◽  
Andrey Gorchakov
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Great Promise ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Biological Features ◽  
Car T Cell Therapy ◽  
Car T ◽  
Antitumor Properties

The adoptive transfer of allogeneic CAR NK cells holds great promise as an anticancer modality due to the relative ease of manufacturing and genetic modification of NK cells, which translates into affordable pricing. Compared to the pronounced efficacy of CAR T cell therapy in the treatment of B cell malignancies, rigorous clinical and preclinical assessment of the antitumor properties of CAR NK cells has been lagging behind. In this brief review, we summarize the biological features of NK cells that may help define the therapeutic niche of CAR NK cells as well as create more potent NK cell-based anticancer products. In addition, we compare T cells and NK cells as the carriers of CARs using the data of single-cell transcriptomic analysis.

scholarly journals Identification of the risks in CAR T-cell therapy clinical trials in China: a Delphi study

2020 ◽  
Vol 12 ◽  
pp. 175883592096657
Author(s):  
Weijia Wu ◽  
Yan Huo ◽  
Xueying Ding ◽  
Yuhong Zhou ◽  
Shengying Gu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Delphi Method ◽  
Delphi Study ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Aims: Within the past few years, there has been tremendous growth in clinical trials of chimeric antigen receptor (CAR) T-cell therapies. Unlike those of many small-molecule pharmaceuticals, CAR T-cell therapy clinical trials are fraught with risks due to the use of live cell products. The aim of this study is to reach a consensus with experts on the most relevant set of risks that practically occur in CAR T-cell therapy clinical trials. Methods: A Delphi method of consensus development was used to identify the risks in CAR T-cell therapy clinical trials, comprising three survey rounds. The expert panel consisted of principal investigators, clinical research physicians, members of institutional ethics committees, and Good Clinical Practice managers. Results: Of the 24 experts invited to participate in this Delphi study, 20 participants completed Round 1, Round 2, and Round 3. Finally, consensus (defined as >80% agreement) was achieved for 54 risks relating to CAR T-cell clinical trials. Effective interventions related to these risks are needed to ensure the proper protection of subject health and safety. Conclusion: The Delphi method was successful in gaining a consensus on risks relevant to CAR T-cell clinical trials in a geographically diverse expert association. It is hoped that this work can benefit future risk-based quality management in clinical trials and can potentially promote the better development of CAR T-cell therapy products.

scholarly journals Chimeric Antigen Receptor Cell Therapy: Overcoming Obstacles to Battle Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 842 ◽  
Author(s):  
Amy J. Petty ◽  
Benjamin Heyman ◽  
Yiping Yang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Clinical Success ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Local Immunosuppression ◽  
Car T

Chimeric antigen receptors (CAR) are fusion proteins engineered from antigen recognition, signaling, and costimulatory domains that can be used to reprogram T cells to specifically target tumor cells expressing specific antigens. Current CAR-T cell technology utilizes the patient’s own T cells to stably express CARs and has achieved exciting clinical success in the past few years. However, current CAR-T cell therapy still faces several challenges, including suboptimal persistence and potency, impaired trafficking to solid tumors, local immunosuppression within the tumor microenvironment and intrinsic toxicity associated with CAR-T cells. This review focuses on recent strategies to improve the clinical efficacy of CAR-T cell therapy and other exciting CAR approaches currently under investigation, including CAR natural killer (NK) and NKT cell therapies.

scholarly journals CAR-T Cell Therapy: Mechanism, Management, and Mitigation of Inflammatory Toxicities

2021 ◽  
Vol 12 ◽  
Author(s):  
Joseph W. Fischer ◽  
Nirjal Bhattarai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Future Research ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Safety Risks ◽  
Car T Cell Therapy ◽  
Car T

Engineered T cell therapies such as chimeric antigen receptor (CAR) expressing T cells (CAR-T cells) have great potential to treat many human diseases; however, inflammatory toxicities associated with these therapies present safety risks and can greatly limit its widespread use. This article briefly reviews our current understanding of mechanisms for inflammatory toxicities during CAR T-cell therapy, current strategies for management and mitigation of these risks and highlights key areas of knowledge gap for future research.

scholarly journals Chimeric antigen receptor T cell therapy in cancer: Advances and challenges

2021 ◽  
Vol 3 (3) ◽  
pp. 46-47
Author(s):  
Yuanzheng Liang ◽  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Number Of Patients ◽  
Car T

Chimeric antigen receptor (CAR) T-cell therapy has drawn the most attention ever in the treatment of hematologic malignancies due to its impressive efficacy in heavily pretreated patients. However, the use of CAR T-cell therapy has just started in the field of solid tumor. Till now, four CAR T-cell therapies have been approved in the world, and an increasing number of patients will receive this expensive treatment. Thus, we will briefly talk about the advances and challenges in the adventure of CAR T-cell therapy

What is CAR T-cell therapy?

2021 ◽  
Vol 59 (5) ◽  
pp. 73-76
Author(s):  
Kayleigh Kew
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Healthcare Professionals ◽  
Cancer Therapeutics ◽  
Current Evidence ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

The emergence of targeted and precision therapies has increased treatment options for people living with cancer. Of particular note is the development and approval of chimeric antigen receptor (CAR) T-cell therapies that involve the use of a patient’s own immune system to treat cancers that have proven resistant to other approaches. Keeping abreast of treatment changes and practice guidelines is a challenge for all healthcare professionals, and the pressure of doing so becomes most acute with innovations in cancer therapeutics that have the potential to extend or save lives. Though uncommon, step changes like CAR T-cell therapy pose a challenge, often requiring completely new ways of thinking about efficacy evidence, basic science, ethics and service delivery. At a time when patients are able and empowered to readily access information about novel and exploratory treatments, healthcare professionals need to feel informed enough to help patients with life-changing or life-limiting cancers who approach them for advice. This article gives an overview of the basic principles of CAR T-cell therapy including how it is delivered, who is eligible to receive it in the UK, and a brief outline of current evidence of its efficacy and safety. The information is intended to provide healthcare professionals with an introduction to CAR T-cell therapy to help them advise potentially eligible patients or those already undergoing treatment about what to expect.

scholarly journals Expanding the Role of CAR-T Cell Therapy to Systemic Lupus Erythematosus

2020 ◽  
pp. 105-112
Author(s):  
Shreya Patel ◽  
Kelly Brassil ◽  
Paiboon Jungsuwadee
Keyword(s):  
T Cell ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Current Treatment ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder resulting from autoantibodies produced by B-cell derived plasma cells. Clinical presentation ranges from mild skin rash to multiorgan failure. Regardless of the clinical presentation or severity of the disease, patients with SLE often require life-long treatment. Current treatment recommendations for SLE include hydroxychloroquine, glucocorticoids, immunomodulatory agents, cyclophosphamide, and biologic agents. Despite availability of these agents, the condition of some patients with SLE progressively worsens. With limited treatment options, new and novel therapeutic approaches are needed. Given the active role of B cells in the pathophysiology of SLE, they present an attractive target for therapies evolving in the oncology field. Amongst these, immune effector cell therapies, including chimeric antigen receptor (CAR)-T cell therapy, have proven beneficial in targeting B cells. The eradication of B cells, along with the potential for T cell persistence, has resulted in prolonged remission or stable disease. This review provides an overview of the pathophysiology of SLE; current treatment options, including monoclonal antibodies targeting cluster of differentiation-20 (CD20), CD22, and B cell-activating factor (BAFF); and explores why and how immune effector cell therapies may prove a promising therapeutic option for this patient population, particularly for individuals with refractory disease. Clinical implications from currently approved U.S. Food and Drug Administration (FDA) agents for haematologic malignancies are discussed and provide insight into considerations for applying this therapy to the patient population with SLE in the context of clinical trials.

scholarly journals Editorial on Special Issue “Immunotherapy, Tumor Microenvironment and Survival Signaling”

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 91
Author(s):  
Vita Golubovskaya
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Cell Therapy ◽  
Antigen Expression ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Survival Signaling

Recently, novel types of immunotherapies such as CAR-T cell therapy demonstrated efficacy in leukemia, lymphoma, and multiple myeloma [1–3]. CD19 and BCMA-CAR-T cell therapies were approved by FDA to treat patients with the above diseases. There are still several challenges for CAR-T cell therapy, including safe and effective antigen targets for solid tumors, overcoming a suppressive tumor microenvironment, and loss of antigen expression, among others [4,5][...]

scholarly journals Humanized Mice Are Precious Tools for Preclinical Evaluation of CAR T and CAR NK Cell Therapies

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1915 ◽  
Author(s):  
Rana Mhaidly ◽  
Els Verhoeyen
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Nk Cell ◽  
Humanized Mice ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Therapy Field

Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for hematological malignancies. However, improvements in CAR T-cell therapies are urgently needed since CAR T cell application is associated with toxicities, exhaustion, immune suppression, lack of long-term persistence, and low CAR T-cell tumor infiltration. Major efforts to overcome these hurdles are currently on the way. Incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system and tumor tissue, represent an important fundamental and preclinical research tool. We will focus here on several CAR T and CAR NK therapies that have benefited from evaluation in humanized mice. These models are of great value for the cancer therapy field as they provide a more reliable understanding of sometimes complicated therapeutic interventions. Additionally, they are considered the gold standard with regard to assessment of new CAR technologies in vivo for safety, efficacy, immune response, design, combination therapies, exhaustion, persistence, and mechanism of action prior to starting a clinical trial. They help to expedite the critical translation from proof-of-concept to clinical CAR T-cell application. In this review, we discuss innovative developments in the CAR T-cell therapy field that benefited from evaluation in humanized mice, illustrated by multiple examples.

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