scholarly journals High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy

Blood ◽  
2019 ◽  
Vol 134 (7) ◽  
pp. 636-640 ◽  
Author(s):  
Alexandre V. Hirayama ◽  
Jordan Gauthier ◽  
Kevin A. Hay ◽  
Jenna M. Voutsinas ◽  
Qian Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Follicular Lymphoma ◽  
Phase 1 ◽  
High Rate ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

Abstract Patients with follicular lymphoma (FL) with early relapse after initial chemoimmunotherapy, refractory disease, or histologic transformation (tFL) have limited progression-free and overall survival. We report efficacy and long-term follow-up of 21 patients with relapsed/refractory (R/R) FL (n = 8) and tFL (n = 13) treated on a phase 1/2 clinical trial with cyclophosphamide and fludarabine lymphodepletion followed by infusion of 2 × 106 CD19-directed chimeric antigen receptor–modified T (CAR-T) cells per kilogram. The complete remission (CR) rates by the Lugano criteria were 88% and 46% for patients with FL and tFL, respectively. All patients with FL who achieved CR remained in remission at a median follow-up of 24 months. The median duration of response for patients with tFL was 10.2 months at a median follow-up of 38 months. Cytokine release syndrome occurred in 50% and 39%, and neurotoxicity in 50% and 23% of patients with FL and tFL, respectively, with no severe adverse events (grade ≥3). No significant differences in CAR-T cell in vivo expansion/persistence were observed between FL and tFL patients. CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R FL with or without transformation, with durable remission in a high proportion of FL patients. This trial was registered at clinicaltrials.gov as #NCT01865617.

HIGH RATE OF DURABLE COMPLETE REMISSION IN FOLLICULAR LYMPHOMA AFTER CD19 CAR-T CELL IMMUNOTHERAPY

2019 ◽  
Vol 37 ◽  
pp. 170-171
Author(s):  
A.V. Hirayama ◽  
J. Gauthier ◽  
K.A. Hay ◽  
J.M. Voutsinas ◽  
Q. Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Follicular Lymphoma ◽  
High Rate ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

scholarly journals Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Jiaying Wu ◽  
Fankai Meng ◽  
Yang Cao ◽  
Yicheng Zhang ◽  
Xiaojian Zhu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
T Cell ◽  
Complete Remission ◽  
Central Nervous System Lymphoma ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

AbstractChimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Here, we treated 13 CNSL patients with ASCT sequential CD19/22 CAR T-cell infusion and simultaneously evaluated the clinical efficacy and toxicity. The 13 CNSL patients analyzed included four primary CNSL and nine secondary CNSL patients. Patients 1 and 10, who had complete remission status before enrollment, maintained clinical efficacy without recurrence. Nine of the remaining 11 patients responded to our protocol with a median durable time of 14.03 months, and the overall response and complete remission rate were 81.81% and 54.55%, respectively. No patient suffered grades 3–4 cytokine-release syndrome (CRS), and only patient 10 experienced severe immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, increases in serum ferritin and interleukin-6 levels were often accompanied by CRS and ICANS. After a median follow-up time of 14.20 months, the estimated 1-year progression-free survival and overall survival rates were 74.59% and 82.50%, respectively. Sequential CD19/22 CAR T-cell immunotherapy following ASCT as a novel method for CNSL appears to have encouraging long-term efficacy with relatively manageable side effects.

scholarly journals CARTmath—A Mathematical Model of CAR-T Immunotherapy in Preclinical Studies of Hematological Cancers

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2941
Author(s):  
Luciana R. C. Barros ◽  
Emanuelle A. Paixão ◽  
Andrea M. P. Valli ◽  
Gustavo T. Naozuka ◽  
Artur C. Fassoni ◽  
...  
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
T Cell ◽  
Mouse Models ◽  
In Silico ◽  
Car T Cells ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens, increasing tumor elimination efficiency. In recent years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate in patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable for use as mathematical models. In this work, we develop a three-population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities are considered uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reducing and optimizing the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such an in silico laboratory is an easy-to-run open-source simulator, built on a Shiny R-based platform called CARTmath. It contains the results of this manuscript as examples and documentation. The developed model together with the CARTmath platform have potential use in assessing different CAR-T cell immunotherapy protocols and its associated efficacy, becoming an accessory for in silico trials.

scholarly journals Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2087
Author(s):  
Yuna Jo ◽  
Laraib Amir Ali ◽  
Ju A Shim ◽  
Byung Ha Lee ◽  
Changwan Hong
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
T Cell Immunotherapy

Novel engineered T cells containing chimeric antigen receptors (CAR-T cells) that combine the benefits of antigen recognition and T cell response have been developed, and their effect in the anti-tumor immunotherapy of patients with relapsed/refractory leukemia has been dramatic. Thus, CAR-T cell immunotherapy is rapidly emerging as a new therapy. However, it has limitations that prevent consistency in therapeutic effects in solid tumors, which accounts for over 90% of all cancer patients. Here, we review the literature regarding various obstacles to CAR-T cell immunotherapy for solid tumors, including those that cause CAR-T cell dysfunction in the immunosuppressive tumor microenvironment, such as reactive oxygen species, pH, O2, immunosuppressive cells, cytokines, and metabolites, as well as those that impair cell trafficking into the tumor microenvironment. Next-generation CAR-T cell therapy is currently undergoing clinical trials to overcome these challenges. Therefore, novel approaches to address the challenges faced by CAR-T cell immunotherapy in solid tumors are also discussed here.

scholarly journals CAR T-cell immunotherapy of MET-expressing malignant mesothelioma

2017 ◽  
Vol 6 (12) ◽  
pp. e1363137 ◽  
Author(s):  
Thivyan Thayaparan ◽  
Roseanna M. Petrovic ◽  
Daniela Y. Achkova ◽  
Tomasz Zabinski ◽  
David M. Davies ◽  
...  
Keyword(s):  
T Cell ◽  
Malignant Mesothelioma ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

2021 ◽  
Author(s):  
Jianqing Mi ◽  
Jie Xu ◽  
Jianfeng Zhou ◽  
Weili Zhao ◽  
Zhu Chen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
B Cell Malignancies ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

scholarly journals PanErbB-targeted CAR T-cell immunotherapy of head and neck cancer

2020 ◽  
Vol 20 (9) ◽  
pp. 965-970
Author(s):  
Daniel Larcombe-Young ◽  
Sophie Papa ◽  
John Maher
Keyword(s):  
Head And Neck Cancer ◽  
T Cell ◽  
Head And Neck ◽  
Neck Cancer ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

Chimeric Antigen Receptor T Cell Immunotherapy for Tumor: A Review of Patent Literatures

2019 ◽  
Vol 14 (1) ◽  
pp. 60-69
Author(s):  
Manxue Fu ◽  
Liling Tang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Limiting Factors ◽  
Car T Cells ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy

Background: Chimeric Antigen Receptor (CAR) T cell immunotherapy, as an innovative method for tumor immunotherapy, acquires unprecedented clinical outcomes. Genetic modification not only provides T cells with the antigen-binding function but also endows T cells with better immunological functions both in solid and hematological cancer. However, the CAR T cell therapy is not perfect because of several reasons, such as tumor immune microenvironment, and autologous limiting factors of CAR T cells. Moreover, the safety of CAR T cells should be improved.Objective:Recently many patents and publications have reported the importance of CAR T cell immunotherapy. Based on the patents about CAR T cell immunotherapy, we conclude some methods for designing the CAR which can provide information to readers.Methods:In this review, we collect recent patents and publications, summarize some specific antigens for oncotherapy from patents and enumerate some approaches to conquering immunosuppression and reinforcing the immune response of CAR T cells. We also sum up some strategies for improving the safety of CAR T cell immunotherapy.Results:CAR T cell immunotherapy as a neotype cellular immunotherapy has been proved effective in oncotherapy and authorized by FDA. Improvements in CAR designing enhance functions of CAR T cells.Conclusion:This review, summarizing antigens and approaches to overcome defects of CAR T cell immunotherapy from patents and publications, might contribute to a broad readership.

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