A guide to cancer immunotherapy: from T cell basic science to clinical practice

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(11), P. 651 - 668

Published: May 20, 2020

Language: Английский

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CAR-T cell therapy: current limitations and potential strategies

Blood Cancer Journal, Journal Year: 2021, Volume and Issue: 11(4)

Published: April 6, 2021

Abstract Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses certain subsets of B leukemia or lymphoma, many challenges limit the therapeutic efficacy solid tumors and hematological malignancies. Barriers to effective include severe life-threatening toxicities, modest anti-tumor activity, escape, restricted trafficking, limited tumor infiltration. In addition, host microenvironment interactions critically alter function. Furthermore, complex workforce required develop implement these treatments. order overcome significant challenges, innovative strategies approaches engineer more powerful improved activity decreased toxicity are necessary. this review, we discuss recent innovations engineering improve both malignancy limitations tumors.

Language: Английский

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Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study

The Lancet Oncology, Journal Year: 2019, Volume and Issue: 21(2), P. 207 - 221

Published: Dec. 16, 2019

Language: Английский

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Long-term outcomes following CAR T cell therapy: what we know so far

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(6), P. 359 - 371

Published: April 13, 2023

Language: Английский

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Recent advances and discoveries in the mechanisms and functions of CAR T cells

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(3), P. 145 - 161

Published: Jan. 22, 2021

Language: Английский

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CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(8), P. 1419 - 1431

Published: July 26, 2021

Abstract Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten 16 large B cell lymphoma (LBCL) disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated To prevent relapse − lo disease, we tested a bispecific CAR targeting and/or CD22 (CD19-22.BB.z-CAR) in phase I clinical trial ( NCT03233854 ) adults relapsed/refractory acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility safety secondary efficacy point. Primary met; 97% products met protocol-specified dose no dose-limiting toxicities occurred during escalation. In B-ALL n = 17), 100% responded 88% minimal residual disease-negative complete remission (CR); LBCL 21), 62% 29% CR. Relapses −/lo (5 out 10) (4 14) but not CD19/22-CAR demonstrated reduced cytokine production when stimulated versus Our results further implicate loss as major cause resistance, highlight the challenge engineering multi-specific equivalent potency across targets identify an important quality indicator for potency.

Language: Английский

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Tuning the Antigen Density Requirement for CAR T-cell Activity

Cancer Discovery, Journal Year: 2020, Volume and Issue: 10(5), P. 702 - 723

Published: March 19, 2020

Abstract Insufficient reactivity against cells with low antigen density has emerged as an important cause of chimeric receptor (CAR) T-cell resistance. Little is known about factors that modulate the threshold for recognition. We demonstrate CD19 CAR activity dependent upon and construct in axicabtagene ciloleucel (CD19-CD28ζ) outperforms tisagenlecleucel (CD19-4-1BBζ) antigen-low tumors. Enhancing signal strength by including additional immunoreceptor tyrosine-based activation motifs (ITAM) enables recognition low-antigen-density cells, whereas ITAM deletions blunt increase threshold. Furthermore, replacement CD8 hinge-transmembrane (H/T) region a 4-1BBζ CD28-H/T lowers despite identical signaling molecules. CARs incorporating more stable efficient immunologic synapse. Precise design can tune endow 4-1BBζ-CARs enhanced capacity to recognize targets while retaining superior persistence. Significance: Optimal on density, which variable many cancers, lymphoma solid CD28ζ-CARs outperform when low. However, be reengineered enhance tumors maintaining their unique This article highlighted In Issue feature, p. 627

Language: Английский

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B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches

Leukemia, Journal Year: 2020, Volume and Issue: 34(4), P. 985 - 1005

Published: Feb. 13, 2020

Despite considerable advances in the treatment of multiple myeloma (MM) last decade, a substantial proportion patients do not respond to current therapies or have short duration response. Furthermore, these treatments can notable morbidity and are uniformly tolerated all patients. As there is no cure for MM, eventually become resistant therapies, leading development relapsed/refractory MM. Therefore, an unmet need exists MM with novel mechanisms action that provide durable responses, evade resistance prior and/or better tolerated. B-cell maturation antigen (BCMA) preferentially expressed by mature B lymphocytes, its overexpression activation associated preclinical models humans, supporting potential utility as therapeutic target Moreover, use BCMA biomarker supported prognostic value, correlation clinical status, ability be used traditionally difficult-to-monitor patient populations. Here, we review three common modalities MM: bispecific antibody constructs, antibody-drug conjugates, chimeric receptor (CAR)-modified T-cell therapy. We overview preliminary data from trials using including BiTE® (bispecific engager) immuno-oncology therapy AMG 420, conjugate GSK2857916, several CAR agents bb2121, NIH CAR-BCMA, LCAR-B38M. Notable antimyeloma activity high minimal residual disease negativity rates been observed treatments. These outline BCMA-targeted improve landscape Importantly, results date suggest may hold promise deep responses support further investigation earlier lines treatment, newly diagnosed

Language: Английский

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The Emerging Landscape of Immune Cell Therapies

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 46 - 62

Published: April 1, 2020

Language: Английский

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CAR immune cells: design principles, resistance and the next generation

Nature, Journal Year: 2023, Volume and Issue: 614(7949), P. 635 - 648

Published: Feb. 22, 2023

Language: Английский

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