Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage?

Kanwal, Bushra

doi:10.7759/cureus.16307

Cited by 3 publications

(3 citation statements)

References 18 publications

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“…CAR T cells represent a cutting-edge immunotherapeutic approach that has revolutionized cancer treatment. Currently, the U.S. Food and Drug Administration (FDA) has approved four autologous CD19-directed CAR T cell therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, high-grade B cell lymphoma, and transformed follicular lymphoma, 49 as well as one autologous B cell maturation antigen (BCMA)-directed CAR T cell therapy for the treatment of relapsed/refractory MM. 50 Despite the successes of CAR T cell therapy in the clinic, several challenges remain unaddressed.…”

Section: Car-engineered Nk-92 and Hank Cellsmentioning

confidence: 99%

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

Fabian

Hodge

2021

Molecular Therapy - Oncolytics

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Natural killer (NK) cells are innate lymphocytes that recognize and clear infected and transformed cells. The importance of NK cells in tumor surveillance underlies the development of NK cell therapy as cancer treatment. The NK-92 cell line has been successfully modified to express high-affinity CD16 receptor for antibody-dependent cellular cytotoxicity and/or chimeric antigen receptors (CARs) that can recognize antigens expressed on tumor cells and mediate NK cell activation. Since there is no need for human leukocyte antigen matching or prior exposure to the tumor antigens, NK-92 provides an opportunity for the development of next-generation off-the-shelf cell therapy platforms. CAR-engineered NK-92 cells have demonstrated robust antitumor activity in in vitro and in vivo preclinical studies, propelling the clinical development of CAR NK-92 cells. Preliminary phase 1 data indicate that CAR NK-92 can be safely administered in the clinic. In this review, we provide an overview of recent advances in the research and clinical application of this novel cell immunotherapy.

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Section: Car-engineered Nk-92 and Hank Cellsmentioning

confidence: 99%

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

Fabian

Hodge

2021

Molecular Therapy - Oncolytics

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“…CAR received impressive remissions, with complete remission (CR) rate 81% (Roex et al, 2020). Compared with favorable results in ALL, the therapeutic effect of CD19 CAR-T in CLL and NHL was dissatisfactory (Kanwal, 2021;Mancikova and Smida, 2021;Myers et al, 2021;Yin et al, 2021). Food and Drug Administration (FDA) approved four autologous CD19-directed CAR-T cell treatments for R/R lymphoma (Ti et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Overall response rate (ORR) ranged from 53.1% to 87%, with CR rates ranging from 39.5% to 62%. Meanwhile, grade 3 or higher cytokine release syndrome (CRS) occurred in 10% to 46% of the individuals (Kanwal, 2021). On-target effects caused by CAR-T cell binding cause CRS, which is a series of hazardous side effects (Cosenza et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

Chen

Liu

Chen

et al. 2022

Sci. China Life Sci.

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CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). CD19− relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome.CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients' primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.

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Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy

Chehelgerdi,

Khorramian-Ghahfarokhi

et al. 2024

Mol Cancer

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The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.

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Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage?

Cited by 3 publications

References 18 publications

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy

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