Finding new lanes: Chimeric antigen receptor (CAR) T‐cells for myeloid leukemia

Pratap, Suraj; Zhao, Zhizhuang Joe

doi:10.1002/cnr2.1222

Cited by 4 publications

(3 citation statements)

References 71 publications

(82 reference statements)

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“…have shown that the combination of anti-CD19 CAR-T-cell therapy with the TKI dasatinib can potentially provide a curative therapy option even in the phenomenon of multilinear disease with several lines of mutated cells present ( 220 ). While several studies have shown substantial success in middle- to long-term follow-up of treated patients, the current research landscape on CAR-T cells focuses on other malignancies due to the success of TKI therapy ( 221 ).…”

Section: Discussionmentioning

confidence: 99%

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Karsten,

Matrisch,

Cichutek

et al. 2023

Front. Immunol.

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Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström’s macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.

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Section: Discussionmentioning

confidence: 99%

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Karsten,

Matrisch,

Cichutek

et al. 2023

Front. Immunol.

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“…It belongs to the family of immunotherapies which share the concept of directing the patients' immune system against the tumor by releasing breaks of immune regulation and suppression (immune checkpoint inhibition), by boosting an immune response using signaling molecules (cytokine therapy), or by infusion of adapted immune cells to optimally target and dispose the malignant cells (cellular immunotherapy, tumor-infiltrating lymphocytes, and cancer vaccine therapy) (1). Specialized T cells with CAR have proven efficacy in therapy of diverse hematopoietic and lymphatic malignancies such as leukemia (2,3), myelomas (4,5) and lymphomas (6)(7)(8). CAR-T cells are characterized by receptor proteins that have been engineered to target binding partners as specific as possible for a particular disease, for example CD19 for therapy of B cell lymphoma.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional states of CAR-T infusion relate to neurotoxicity – lessons from high-resolution single-cell SOM expression portraying

Loeffler‐Wirth

Rade²,

Arakelyan³

et al. 2022

Front. Immunol.

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Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for patients with B cell lymphomas, however it copes with partly severe adverse effects like neurotoxicity. Single-cell resolved molecular data sets in combination with clinical parametrization allow for comprehensive characterization of cellular subpopulations, their transcriptomic states, and their relation to the adverse effects. We here present a re-analysis of single-cell RNA sequencing data of 24 patients comprising more than 130,000 cells with focus on cellular states and their association to immune cell related neurotoxicity. For this, we developed a single-cell data portraying workflow to disentangle the transcriptional state space with single-cell resolution and its analysis in terms of modularly-composed cellular programs. We demonstrated capabilities of single-cell data portraying to disentangle transcriptional states using intuitive visualization, functional mining, molecular cell stratification, and variability analyses. Our analysis revealed that the T cell composition of the patient’s infusion product as well as the spectrum of their transcriptional states of cells derived from patients with low ICANS grade do not markedly differ from those of cells from high ICANS patients, while the relative abundancies, particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR positive cells, vary. Our study provides molecular details of the transcriptomic landscape with possible impact to overcome neurotoxicity.

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“…[9,10] Chronic myeloid leukemia is an indolent disease that requires lifelong treatment and affects mostly adults, while CLL as the most prevalent form of leukemia in adults accounts for onethird of all leukemias in Western countries. [11,12] The survival of patients with leukemia drastically improved in recent years as the therapeutic landscape for leukemia has significantly evolved. [13,14] However, chemoresistance and relapse due to the survival mechanisms utilized by leukemic cells are common, and leukemia is projected to account for an increased 470,000 deaths in 2040 if the current trends continue.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

Yang¹,

Xuan²,

Li³

et al. 2022

Archiv der Pharmazie

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Leukemia, a hematological malignancy originating from the bone marrow, is the principal cancer of childhood. In recent decades, improved remission rates and survival of patients with leukemia have been achieved due to significant breakthroughs in the treatment. However, chemoresistance and relapse are common, creating an urgent need for the search for novel pharmaceutical interventions. 1,2,3‐Triazole is one of the most fascinating pharmacophores in the discovery of new drugs, and several 1,2,3‐triazole derivatives have already been used in clinics or are under clinical evaluation for the treatment of cancers. In particular, 1,2,3‐triazole hybrids could suppress tumor proliferation, invasion, and metastasis by inhibiting enzymes, proteins, and receptors in cancer cells, revealing their potential as putative antileukemic agents. This review covers the recent advances regarding the 1,2,3‐triazole hybrids with potential antileukemic activity, focusing on the chemical structures, structure–activity relationship, and mechanisms of action, covering articles published from January 2017 to January 2022.

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Finding new lanes: Chimeric antigen receptor (CAR) T‐cells for myeloid leukemia

Cited by 4 publications

References 71 publications

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Broadening the horizon: potential applications of CAR-T cells beyond current indications

Transcriptional states of CAR-T infusion relate to neurotoxicity – lessons from high-resolution single-cell SOM expression portraying

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

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