Chimeric Antigen Receptor T‐Cells: Successful Translation of the First Cell and Gene Therapy From Bench to Bedside

Rodriguez-Cartagena, Luis G.; Bowles, Bradley S.; Kurani, Shaheen; Windebank, Anthony J.; Kenderian, Saad S.; Greenberg, Alexandra J.

doi:10.1111/cts.12586

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Kymriah®, approved by the FDA in 2017, was the first T‐cell therapy available in the United States 36 . Kymriah® is indicated for the treatment of children and young adults with r/r B‐cell precursor acute lymphoblastic leukemia (r/r B cell ALL) and adult patients with certain types of r/r large B‐cell lymphoma after the failure of at least two lines of systemic therapy.…”

Section: Clinically Approved Productsmentioning

confidence: 99%

Cell therapies in the clinic

Wang

Janes

Kumbhojkar

et al. 2021

Bioengineering & Transla Med

102

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Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes. As such, cell therapies are currently one of the most investigated therapeutic modalities in both preclinical and clinical settings, with many products having been approved and many more under active clinical investigation. Here, we highlight the diversity and key advantages of cell therapies and discuss their current clinical advances. In particular, we review 28 globally approved cell therapy products and their clinical use. We also analyze >1700 current active clinical trials of cell therapies, with an emphasis on discussing their therapeutic applications. Finally, we critically discuss the major biological, manufacturing, and regulatory challenges associated with the clinical translation of cell therapies.

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Section: Clinically Approved Productsmentioning

confidence: 99%

Cell therapies in the clinic

Wang

Janes

Kumbhojkar

et al. 2021

Bioengineering & Transla Med

102

View full text Add to dashboard Cite

show abstract

“…Later, scientists began to think about whether new immunotherapy could be invented that would not cause any secondary disease in the patient. Next, they think about T cell immunotherapy which they later genetically modify in the lab, expand and then infuse into the patient's body [22]. From their thinking, this immunotherapy is experimented in different sites and modified after a certain time interval, and finally comes to today's position, CAR T cell immunotherapy, which is accepted by the US FDA.…”

Section: History Of Car T Cellmentioning

confidence: 99%

CAR T Cell Immunotherapy That Revolutionary Breakthrough in Human Oncology Treatment: A Review

Bashar¹,

Akhter²,

Saha³

et al. 2022

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Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells

Lee

Cheung

et al. 2021

Molecular Cancer Therapeutics

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Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major cause of relapse. The origins of relapse in AML have been traced to rare therapy-resistant leukemic stem cells (LSCs) that are already present at diagnosis. Effective treatment strategies for long-term remission are lacking, as it has been difficult to eliminate LSCs with conventional therapy. Here, we proposed a new approach based on the chimeric antigen receptor (CAR)-directed T lymphocytes, targeting T-cell immunoglobulin, and mucin domain 3 (TIM-3) to treat MRD in patients with AML. TIM-3 is selected as the target because it is highly expressed on AML blasts and LSCs in most subtypes regardless of the patient's genetic characteristics and treatment course. Moreover, it is absent in the normal hematopoietic stem cells, granulocytes, naïve lymphocytes, and most normal nonhematopoietic tissues. Using a naïve human Fab phage display library, we isolated an anti-human TIM-3 antibody and designed a second-generation anti–TIM-3. Our anti–TIM-3 CAR T cells exhibit potent antileukemic activity against AML cell lines and primary AML blasts, and in the mouse models. More importantly, we demonstrate efficient killing of the primary LSCs directly isolated from the patients. Hence, eradication of the LSCs present in the MRD by anti–TIM-3 CAR T-cell therapy following the first-line treatment may improve the clinical outcomes of patients with AML.

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Chimeric Antigen Receptor T‐Cells: Successful Translation of the First Cell and Gene Therapy From Bench to Bedside

Cited by 3 publications

References 9 publications

Cell therapies in the clinic

Cell therapies in the clinic

CAR T Cell Immunotherapy That Revolutionary Breakthrough in Human Oncology Treatment: A Review

Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells

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