A new vision of the efficacy of both CAR-NK and CAR-T cells in treating cancers and autoimmune diseases

Medical Oncology, Journal Year: 2024, Volume and Issue: 41(6)

Published: April 24, 2024

Language: Английский

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A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 27, 2023

Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR targeting CD22, as well dual-targeting CD19/CD22 T-cells, currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate efficacy safety CD22-targeting T-cell therapies. We searched MEDLINE, EMBASE, Web Science, Cochrane Central Register Controlled Trials from inception March 3rd 2022 full-length articles conference abstracts trials employing acute lymphocytic leukemia (ALL) non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian Laird random-effects model with arcsine transformation used pool proportions. From 1068 references screened, 100 were included, representing 30 early phase studies 637 patients, investigating CD22 or T-cells. had a bCR 68% [95% CI, 53-81%] ALL (n= 116), 64% 46-81%] NHL 28) 74% 96% patients having received anti-CD19 previously respectively. rate 90% 84-95%] 297) 47% 34-61%] 137). estimated incidence total severe (grade ≥3) CRS 87% 80-92%] 6% 3-9%] ICANS 16% 9-25%] 3% 1-5%] Early show high remission rates NHL. Severe (1)rare did not increase toxicity. Variability construct, dose, patient factors amongst limits comparisons, long-term outcomes yet be reported. Systematic registration https://www.crd.york.ac.uk/prospero , identifier CRD42020193027.

Language: Английский

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Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update

Current Oncology, Journal Year: 2023, Volume and Issue: 30(9), P. 8501 - 8549

Published: Sept. 15, 2023

Glioblastoma is the most common malignant primary brain tumor in adults. The prognosis extremely poor even with standard treatment of maximal safe resection, radiotherapy, and chemotherapy. Recurrence inevitable within months, options are very limited. Chimeric antigen receptor T-cell therapy (CART) bispecific engagers (TCEs) two emerging immunotherapies that can redirect T-cells for tumor-specific killing have shown remarkable success hematological malignancies been under extensive study application glioblastoma. While there multiple clinical trials showing preliminary evidence safety efficacy CART, TCEs still early stages testing, preclinical studies promising results. However, shared challenges need to be addressed future, including route delivery, escape, immunosuppressive microenvironment, toxicity resulting from limited choice antigens. Efforts underway optimize design both these treatments find ideal combination overcome challenges. In this review, we describe work has performed as well novel approaches glioblastoma other solid tumors may applicable future.

Language: Английский

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Alternative target recognition elements for chimeric antigen receptor (CAR) T cells: beyond standard antibody fragments

Cytotherapy, Journal Year: 2024, Volume and Issue: 26(7), P. 729 - 738

Published: March 2, 2024

Background aimsChimeric antigen receptor T (CAR-T) cells are a remarkably efficacious, highly promising and rapidly evolving strategy in the field of immuno-oncology. The precision these targeted cellular therapies is driven by specificity recognition element (the "binder") encoded CAR. This binder redirects immune effector precisely toward defined on surface cancer cells, leading to T-cell receptor–independent tumor lysis. Currently, for targeting most CAR-T designed using single-chain variable fragments (scFvs) derived from murine or human immunoglobulins. However, there several emerging alternative modalities that finding increasing utility improved CAR function beyond scFvs.MethodsHere we review recent developments use non-canonical protein binding domains design, including nanobodies, DARPins, natural ligands, de novo–designed elements.ResultsOverall, describe how new formats, with their unique structural properties mechanisms action, may possess key advantages over traditional scFv designs.ConclusionsThese designs contribute enhanced therapeutic options and, ultimately, outcomes patients.

Language: Английский

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Chimeric antigen receptor (CAR) modified T Cells in acute myeloid leukemia: limitations and expectations

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 17, 2024

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a poor prognosis despite the advent of novel therapies. Consequently, major need exists for new therapeutic options, particularly patients relapsed/refractory (R/R) AML. In recent years, it has been possible to individualize treatment subgroup patients, emergence multiple targeted Nonetheless, considerable number remain without and overall remains because high rate disease relapse. this sense, cellular therapies, especially chimeric antigen receptor (CAR)-T cell therapy, have dramatically shifted options other malignancies, such as diffuse large B lymphoma acute lymphoblastic leukemia. contrast, effectively treating AML CAR-based immunotherapy poses biological clinical challenges, most them derived from unmet identify target antigens expression restricted blast compromising viability normal hematopoietic stem counterpart. Although those limitations hampered CAR-T therapy translation clinic, there are several trials where antigens, CD123, CLL-1 or CD33 being used treat showing promising results. Moreover, continuing efforts enhance specificity efficacy in These endeavors encompass exploration avenues, including development dual cells next-generation cells, well utilization gene editing tools mitigate off-tumor toxicities. review, we will summarize ongoing studies early results reported AML, highlight approaches overcome these barriers. We also discuss how when should be context

Language: Английский

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Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2243 - 2243

Published: June 17, 2024

Since the introduction of rituximab in late 1990s, significant progress has been made advancing targeted therapies for B cell lymphomas, improving patients’ chance being cured and clinicians’ therapeutic armamentarium. A better understanding disease biology pathogenic pathways, coupled with refinements immunophenotypic molecular diagnostics, have instrumental these achievements. While traditional chemotherapy remains fundamental most cases, concerns surrounding chemorefractoriness cumulative toxicities, particularly depletion hemopoietic reserve, underscore imperative personalized treatment approaches. Integrating agents, notably monoclonal antibodies, alongside yielded heightened response rates prolonged survival. notable paradigm shift is underway innovative-targeted replacing cytotoxic drugs, challenging conventional salvage strategies like stem transplantation. This review examines landscape emerging targets lymphoma cells explores innovative diffuse large (DLBCL). From Chimeric Antigen Receptor-T to more potent antibody–drug conjugates, bispecific checkpoint inhibitors, small molecules targeting intracellular each modality offers promising avenues advancement. aims furnish insights into their potential implications future DLBCL strategies.

Language: Английский

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CAR-T in the Treatment of Acute Myeloid Leukemia: Barriers and How to Overcome Them

HemaSphere, Journal Year: 2023, Volume and Issue: 7(9), P. e937 - e937

Published: Aug. 18, 2023

Conventional therapies for acute myeloid leukemia (AML) are characterized by high rates of relapse, severe toxicities, and poor overall survival rates. Thus, the development new therapeutic strategies is crucial improving quality life AML patients. CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy has been extremely successful in treatment B-cell lymphoid several mature lymphomas. However, use CAR therapy currently prevented due to lack a equivalent CD19, as known cell surface targets on leukemic blasts also expressed healthy hematopoietic stem progenitor cells well their progeny. In addition, immunosuppressive tumor microenvironment dampening effect antitumor activity CAR-T cells. Here, we review challenges limiting discuss promising novel overcome them.

Language: Английский

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In Situ Programming of CAR-T Cells: A Pressing Need in Modern Immunotherapy

Archivum Immunologiae et Therapiae Experimentalis, Journal Year: 2023, Volume and Issue: 71(1)

Published: July 7, 2023

Abstract Chimeric antigen receptor-T (CAR-T) cell-based therapy has become a successful option for treatment of numerous hematological malignancies, but also raises hope in range non-malignant diseases. However, traditional approach, generation CAR-T cells is associated with the separation patient’s lymphocytes, their vitro modification, and expansion infusion back into bloodstream. This classical protocol complex, time-consuming, expensive. Those problems could be solved by protocols to produce cells, CAR-natural killer or CAR macrophages, situ, using viral platforms non-viral delivery systems. Moreover, it was demonstrated that situ induction may reduced risk most common toxicities therapy, such as cytokine release syndrome, immune effector cell-associated neurotoxicity “on-target, off-tumor” toxicity. review aims summarize current state-of-the-art future perspectives situ-produced cells. Indeed, preclinical work this area, including animal studies, prospective translational development validation practical medicine strategies CAR-bearing

Language: Английский

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Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities

European Journal Of Haematology, Journal Year: 2023, Volume and Issue: 112(2), P. 197 - 210

Published: Aug. 6, 2023

The success of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer truly personalized fashion. Second generation receptors (CAR) incorporating co-stimulatory molecules like 4-1BB or CD28 were able overcome some hindrances with initial CAR constructs resulting efficacious products. Many second-generation CAR-T products have been approved treatment relapsed/refractory including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain optimizing manufacturing, timely access, limiting toxicity from infusions improving sustainability responses derived therapy. Here, we summarize clinical trial data leading approval therapies MM NHL, discuss limitations current strategies review emerging for overcoming these limitations.

Language: Английский

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Different Strategies to Overcome Resistance to Proteasome Inhibitors—A Summary 20 Years after Their Introduction

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8949 - 8949

Published: Aug. 16, 2024

Proteasome inhibitors (PIs), bortezomib, carfilzomib, and ixazomib, are the first-line treatment for multiple myeloma (MM). They inhibit cytosolic protein degradation in cells, which leads to accumulation of misfolded malfunctioned proteins cytosol endoplasmic reticulum, resulting cell death. Despite being a breakthrough MM therapy, malignant cells develop resistance PIs via different mechanisms. Understanding these mechanisms drives research toward new anticancer agents overcome PI resistance. In this review, we summarize mechanism action how adapt drugs Finally, explore present strategies interfere with The include ubiquitin-proteasome system, drug efflux inhibitors, autophagy disruption, targeting stress response mechanisms, affecting survival cycle regulators, bone marrow microenvironment modulation, immunotherapy. We list potential pharmacological targets examined vitro, vivo, clinical studies. Some have already provided clinicians anti-MM medications, such as panobinostat selinexor. hope that further exploration subject will broaden range therapeutic options improve patient outcomes.

Language: Английский

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