Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors

Jung, In-Young; Noguera-Ortega, Estela; Collins, Sierra M.; Williams, Erik F.; Davis, Megan M.; Jadlowsky, Julie K.; Plesa, Gabriela; Siegel, Donald L.; Chew, Anne; Levine, Bruce L.; Berger, Shelley L.; Moon, Edmund K.; Albelda, Steven Μ.; Fraietta, Joseph A.

doi:10.1016/j.xcrm.2023.101053

Cited by 20 publications

(7 citation statements)

References 90 publications

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“…In summary, the study by Jung et al. 1 demonstrates that small tweaks in the CAR T cell manufacturing protocol can generate T RM CAR T cells with enhanced ability to penetrate solid tumors and resist functional exhaustion. While additional pre-clinical testing is warranted, CAR T cell priming with TGF-β has shown promise to easily manipulate CAR T cell functionality with potentially easy translation to the clinic.…”

Section: Main Textmentioning

confidence: 97%

“…et al. 1 developed a method by which CAR T cell products can be enriched for tissue-resident memory (T RM ) phenotypes to encourage CAR T cell accumulation in tumor tissue. While many blood cancers benefit from CAR T cells that actively circulate through the bloodstream and bone marrow, effective treatment of solid tumors requires cellular programming that encourages cytolytic CAR T cells to persist at the location of a tumor and resist recirculation.…”

Section: Main Textmentioning

confidence: 99%

“…Jung et al. 1 demonstrate enrichment of resident memory phenotypes through simple changes to the CAR T cell manufacturing process.…”

mentioning

confidence: 99%

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Steering CAR T cell epigenetic programs by tweaking manufacturing protocol

Dukes

Krenciute

2023

Cell Reports Medicine

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Section: Main Textmentioning

confidence: 97%

Section: Main Textmentioning

confidence: 99%

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Steering CAR T cell epigenetic programs by tweaking manufacturing protocol

Dukes

Krenciute

2023

Cell Reports Medicine

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“…To strengthen CAR-T cell functionality and persistence, activation of TGF-β by repetitive challenges can epigenetically reprogram T cells toward a stem-like memory state and promote the robust expansion of human tissue-resident memory CD8 + CAR-T cells (CAR-T RM ), attracting CAR-T cells to accumulate and eventually eliminate solid tumors [ 125 ]. Metabolic strategies were carried out to support T RM differentiation and durable function, and to facilitate tissue residency of memory CD8 + T cells in solid tumors for TIL enrichment, therefore maintaining their effector functions for improved prognosis [ 126 ].…”

Section: Cancer Immunotherapy Involving Cd8 + T Cellsmentioning

confidence: 99%

CD8+ T cell-based cancer immunotherapy

Chen,

Yu,

Qian

et al. 2024

J Transl Med

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The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8+ T cells play a crucial role in opposing pathological threats. Various immunotherapies based on CD8+ T cells have emerged in recent decades, showing their promising results in treating intractable diseases. However, in the fight against the constantly changing and evolving cancers, the formation and function of CD8+ T cells can be challenged by tumors that might train a group of accomplices to resist the T cell killing. As cancer therapy stepped into the era of immunotherapy, understanding the physiological role of CD8+ T cells, studying the machinery of tumor immune escape, and thereby formulating different therapeutic strategies become the imperative missions for clinical and translational researchers to fulfill. After brief basics of CD8+ T cell-based biology is covered, this review delineates the mechanisms of tumor immune escape and discusses different cancer immunotherapy regimens with their own advantages and setbacks, embracing challenges and perspectives in near future.

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“…A recent report suggested that ex vivo expansion of CAR-T cells in the presence of TGF-β could significantly enhance tumor infiltration and efficacy in xenograft tumor models ( 95 ). This approach aimed to epigenetically rewire peripheral blood T cells toward a resident memory T cell phenotype (T RM ), which would enhance accumulation and promote stemness of the transferred CAR-T cells targeting MSLN.…”

Section: Infiltrationmentioning

confidence: 99%

DIALing-up the preclinical characterization of gene-modified adoptive cellular immunotherapies

Giardino Torchia,

Moody

2023

Front. Immunol.

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The preclinical characterization of gene modified adoptive cellular immunotherapy candidates for clinical development often requires the use of mouse models. Gene-modified lymphocytes (GML) incorporating chimeric antigen receptors (CAR) and T-cell receptors (TCR) into immune effector cells require in vivo characterization of biological activity, mechanism of action, and preclinical safety. Typically, this characterization involves the assessment of dose-dependent, on-target, on-tumor activity in severely immunocompromised mice. While suitable for the purpose of evaluating T cell-expressed transgene function in a living host, this approach falls short in translating cellular therapy efficacy, safety, and persistence from preclinical models to humans. To comprehensively characterize cell therapy products in mice, we have developed a framework called “DIAL”. This framework aims to enable an end-to-end understanding of genetically engineered cellular immunotherapies in vivo, from infusion to tumor clearance and long-term immunosurveillance. The acronym DIAL stands for Distribution, Infiltration, Accumulation, and Longevity, compartmentalizing the systemic attributes of gene-modified cellular therapy and providing a platform for optimization with the ultimate goal of improving therapeutic efficacy. This review will discuss both existent and emerging examples of DIAL characterization in mouse models, as well as opportunities for future development and optimization.

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Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors

Cited by 20 publications

References 90 publications

Steering CAR T cell epigenetic programs by tweaking manufacturing protocol

Steering CAR T cell epigenetic programs by tweaking manufacturing protocol

CD8+ T cell-based cancer immunotherapy

DIALing-up the preclinical characterization of gene-modified adoptive cellular immunotherapies

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