scholarly journals Tracking the CAR-T Revolution: Analysis of Clinical Trials of CAR-T and TCR-T Therapies for the Treatment of Cancer (1997–2020)

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1062
Author(s):  
Nikola A. Ivica ◽  
Colin M. Young
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
T Cell Receptor ◽  
Chimeric Antigen Receptor ◽  
Therapeutic Approach ◽  
Cell Receptor ◽  
B Cell Malignancies ◽  
Car T ◽  
The Us ◽  
Robust Response

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR-T) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR-T clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR-T industry may be a robust response to success and failure of competitor products.

scholarly journals Tracking the CAR-T Revolution: Analysis of Clinical Trials of CAR-T and TCR Therapies for the Treatment of Cancer (1997-2020)

2021 ◽  
Author(s):  
Nikola Aleksandar Ivica ◽  
Colin M Young
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
T Cell Receptor ◽  
Chimeric Antigen Receptor ◽  
Therapeutic Approach ◽  
Cell Receptor ◽  
B Cell Malignancies ◽  
Car T ◽  
The Us ◽  
Robust Response

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

scholarly journals Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Komal Adeel ◽  
Nathan J. Fergusson ◽  
Risa Shorr ◽  
Harold Atkins ◽  
Kevin A. Hay
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background Chimeric antigen receptor (CAR) T cell therapy has had great success in treating patients with relapsed or refractory B cell malignancies, with CD19-targeting therapies now approved in many countries. However, a subset of patients fails to respond or relapse after CD19 CAR T cell therapy, in part due to antigen loss, which has prompted the search for alternative antigen targets. CD22 is another antigen found on the surface of B cells. CARs targeting CD22 alone or in combination with other antigens have been investigated in several pre-clinical and clinical trials. Given the heterogeneity and small size of CAR T cell therapy clinical trials, systematic reviews are needed to evaluate their efficacy and safety. Here, we propose a systematic review of CAR T cell therapies targeting CD22, alone or in combination with other antigen targets, in B cell malignancies. Methods We will perform a systematic search of EMBASE, MEDLINE, Web of Science, Cochrane Register of Controlled Trials, clinicaltrials.gov, and the International Clinical Trials Registry Platform. Ongoing and completed clinical trials will be identified and cataloged. Interventional studies investigating CD22 CAR T cells, including various multi-antigen targeting approaches, in patients with relapsed or refractory B cell malignancies will be eligible for inclusion. Only full-text articles, conference abstracts, letters, and case reports will be considered. Our primary outcome will be a complete response, defined as absence of detectable cancer. Secondary outcomes will include adverse events, overall response, minimal residual disease, and relapse, among others. Quality assessment will be performed using a modified Institute of Health Economics tool designed for interventional single-arm studies. We will report a narrative synthesis of clinical studies, presented in tabular format. If appropriate, a meta-analysis will be performed using a random effects model to synthesize results. Discussion The results of the proposed review will help inform clinicians, patients, and other stakeholders of the risks and benefits of CD22 CAR T cell therapies. It will identify gaps or inconsistencies in outcome reporting and help to guide future clinical trials investigating CAR T cells. Systematic review registration PROSPERO registration number: CRD42020193027

scholarly journals The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review

2019 ◽  
Vol 18 ◽  
pp. 153303381983106 ◽  
Author(s):  
Jianxiang Zhang ◽  
Lingyu Wang
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Solid Tumors ◽  
T Cell Receptor ◽  
Chimeric Antigen Receptor ◽  
Hematological Malignancies ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
T Cell Therapy

T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor–engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor–engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor–engineered T-cell therapy’s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor–engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor’s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor–engineered T-cell therapy due to tumor microenvironment were also discussed here.

scholarly journals Immune escape mechanism of B-cell malignancies on Anti-CD19 Chimeric Antigen Receptor T-cell treatment and solution

2021 ◽  
Vol 271 ◽  
pp. 03038
Author(s):  
Jin Qian
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Immune Escape ◽  
B Cell Malignancies ◽  
Escape Mechanism ◽  
Car T Cells ◽  
Car T ◽  
Immune Escape Mechanism

Relapse or refractory B-cell malignancies have been reported in multiple clinical trials after treatment of Anti-CD19 Chimeric Antigen Receptor (CAR) T-cells. Many clinical studies have demonstrated the potential immune escape mechanism for B-cell malignancies like genetic mutation, transcriptional deregulation, lineage switch, loss of CAR T-cells, and trogocytosis. The study of these mechanisms can provide us insights in designs of future immunotherapies regarding both B-cell malignancies and even other solid tumors. The potential solution for the immune escape mechanisms regarding CAR T-cell treatment is engineering multispecific CARs. In this article, I review most of the upto- date immune escape mechanism studies and some multispecific CAR T-cell treatment clinical studies and trials that may prevent the escape route and have to potential to cure B-cell malignancies.

Efficacy and safety of chimeric antigen receptor T cell immunotherapy in B-cell non-Hodgkin lymphoma: a systematic review and meta-analysis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Na Wang ◽  
Yunchong Meng ◽  
Yaohui Wu ◽  
Jing He ◽  
Fang Liu
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Chimeric Antigen Receptor ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T

Aim: The aim was to evaluate the efficacy and safety of chimeric antigen receptor T (CAR-T) cell in B-cell non-Hodgkin lymphoma (B-NHL). Materials & methods: A meta-analysis was conducted using eligible clinical trials, which were obtained from electronic medical literature databases. Results: A total of 24 clinical trials with 590 patients were included. The best overall response rate was 66% and complete remission rate was 46%. The incidence rates of cytokine-release syndrome and neurotoxicity (grade ≥ 3) were 9 and 5%, respectively. The various clinical factors were analyzed. Autogenic CAR-T cell may lead to improved efficacy than allogeneic CAR-T cell. CD20 CAR-T cell may show increased efficacy than CD19 CAR-T cell. Conclusion: CAR-T immunotherapy has remarkable efficacy and low toxicity in relapsed/refractory B-NHL.

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