scholarly journals Chimeric Antigen Receptor T-Cell Therapy: An Overview of the Changing Face of Cancer Immunotherapy

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Pouya Safarzadeh Kozani ◽  
Pooria Safarzadeh Kozani ◽  
Fatemeh Rahbarizadeh
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Cell Lymphoma ◽  
Hematologic Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

: Chimeric antigen receptor (CAR) T-cell therapy has emerged as the revolutionary cancer treatment method in recent years due to the heartwarming clinical outcomes in several types of hematologic malignancies. Since 2017, the US Food and Drug Administration has approved four CAR T-cell products, including tisagenlecleucel [for B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma (DLBCL)], axicabtagene ciloleucel (for DLBCL), brexucabtagene autoleucel (for mantle cell lymphoma), and lisocabtagene maraleucel (for DLBCL). The efficacy optimization and toxicity management methods of CAR T-cell therapy are among the most investigated fields of cancer immunotherapy. Furthermore, the favorable outcomes achieved by the aforementioned CAR T-cell products in hematologic malignancies have encouraged researchers to bring successful outcomes to solid tumor patients. This study aimed to highlight the outstanding characteristics and the manufacturing process of CAR T-cells and discuss the key lane leading to their clinically approved products.

scholarly journals Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5592
Author(s):  
Edit Porpaczy ◽  
Philipp Wohlfarth ◽  
Oliver Königsbrügge ◽  
Werner Rabitsch ◽  
Cathrin Skrabs ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Tp53 Mutation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.

scholarly journals Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions

2021 ◽  
pp. IJH33
Author(s):  
Julio C Chavez ◽  
Farah Yassine ◽  
Jose Sandoval-Sus ◽  
Mohamed A Kharfan-Dabaja
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Current Status ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Aims: To review recent data and relevant of the role of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for B-cell non-Hodgkin lymphoma (NHL). Methods: Review and compilation of the most recent and relevant data published in full text and abstract forms of anti-CD19 CAR T-cell therapy for B-cell NHL. Results: Different anti-CD19 CAR T-cell therapy products have been tested and shown significant clinical activity across B-cell NHL patients. The objective responses in relapsed DLBCL, FL and MCL were 50–83%, 83–93% and 93%, respectively. Conclusions: Anti-CD19 CAR T-cell therapy is a viable option for poor risk refractory B-cell NHLs.

Abstract 3250: CD229-targeted CAR T cell therapy for the treatment of B cell lymphoma

2020 ◽  
Author(s):  
Michael L. Olson ◽  
Sabarinath V. Radhakrishnan ◽  
Tim C. Luetkens ◽  
Djordje Atanackovic
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Adverse Events and Side Effects of Chimeric Antigen Receptor (CAR) T Cell Therapy in Patients with Hematologic Malignancies

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Pooria Safarzadeh Kozani ◽  
Shima Shabani
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Hematologic Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Management Procedures ◽  
Car T

: Chimeric antigen receptor (CAR) T cell therapy is rapidly being established as a new cancer treatment modality especially for the treatment of hematologic malignancies. Alongside being capable of inducing durable responses in such malignancies, CAR T cell therapy has always been accompanied by exclusive toxicities such as cytokine release syndrome (CRS), that can range from mild to life-threatening. These toxicities require intensive monitoring and fast and executive management procedures to reduce the level of damages or the rate of mortality in CAR T cell therapy recipients. In this review, we tend to introduced some of the most common CAR T cell therapy-related toxicities and their clinical demonstrations. Furthermore, we also introduce some of the management procedures commonly considered in this regard.

scholarly journals Salvage Therapy With Polatuzumab Vedotin, Bendamustine, and Rituximab Prior to Allogeneic Hematopoietic Transplantation in Patients With Aggressive Lymphomas Relapsing After Therapy With Chimeric Antigen Receptor T-Cells—Report on Two Cases

2021 ◽  
Vol 11 ◽  
Author(s):  
Kristin Gerhardt ◽  
Madlen Jentzsch ◽  
Thomas Georgi ◽  
Aleksandra Sretenović ◽  
Michael Cross ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Up to 60% of patients with aggressive B-cell lymphoma who receive chimeric antigen receptor (CAR) T-cell therapy experience treatment failure and subsequently have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a potentially curative approach for patients in this situation. Induction of a deep response prior to alloHSCT is crucial for long-term outcomes, but the optimal bridging strategy following relapse after CAR T-cell therapy has not yet been established. Polatuzumab vedotin, an antibody drug conjugate targeting CD79b, is a novel treatment option for use in combination with rituximab and bendamustine (Pola-BR) in relapsed or refractory disease. Patients: We report two heavily pretreated patients with primary refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) respectively who relapsed after therapy with CAR T-cells with both nodal and extranodal manifestations of the disease. After application of three courses of Pola-BR both patients achieved a complete metabolic remission. Both patients underwent alloHSCT from a human leukocyte antigen (HLA)-mismatched donor following conditioning with busulfan and fludarabine and are disease free 362 days and 195 days after alloHSCT respectively. We conclude that Pola-BR can be an effective bridging therapy before alloHSCT of patients relapsing after CAR T-cell therapy. Further studies will be necessary to define the depth and durability of remission of this salvage regimen before alloHSCT.

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