Immunotherapy: a promising approach for glioma treatment

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

Published: Sept. 7, 2023

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being common and aggressive type. Despite two decades of relentless pursuit in exploring novel therapeutic approaches for GBM, there is limited progress improving patients’ survival outcomes. Numerous obstacles impede effective treatment including immunosuppressive tumor microenvironment (TME), blood-brain barrier, extensive heterogeneity. these challenges, immunotherapies emerging as a promising avenue that may offer new hope gliomas. There four main types gliomas, immune checkpoint blockades, chimeric antigen receptor T-cell therapies, vaccines, oncolytic viruses. In addition, gene therapy, bispecific antibody combine therapy also briefly introduced this review. The significant role TME process has been emphasized many studies. Although immunotherapy enormous effort required to overcome existing barriers its success. Owing rapid development increasing attention paid article aims review recent advances

Language: Английский

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Fc-Engineered Therapeutic Antibodies: Recent Advances and Future Directions

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(10), P. 2402 - 2402

Published: Sept. 28, 2023

Monoclonal therapeutic antibodies have revolutionized the treatment of cancer and other diseases. Fc engineering aims to enhance effector functions or half-life by modifying their regions. Recent advances in modern can be considered next generation antibody therapy. Various strategies are employed, including altering glycosylation patterns via glycoengineering introducing mutations region, thereby enhancing receptor complement interactions. Further, enable bispecific IgG-based heterodimeric antibodies. As techniques continue evolve, an expanding portfolio Fc-engineered is advancing through clinical development, with several already approved for medical use. Despite plethora Fc-based that been analyzed vitro vivo models, we focus here this review on relevant finetune functions, modify stabilize asymmetric IgGs.

Language: Английский

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Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 74, P. 101068 - 101068

Published: Feb. 13, 2024

Language: Английский

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Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(734)

Published: Feb. 14, 2024

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)–directed immunotherapy, including T cells bearing chimeric receptors (CARs) systemically injected bispecific engagers (TCEs), has shown remarkable clinical activity, several products have received market approval. However, despite promising results, patients eventually become refractory relapse, highlighting need for alternative strategies. Engineered secreting TCE antibodies (STAb) represent a strategy that combines advantages of adoptive therapies antibodies. Here, we undertook comprehensive preclinical study comparing therapeutic potential either expressing second-generation anti-BCMA CARs (CAR-T) or BCMAxCD3 TCEs (STAb-T) cell–limiting experimental setting mimicking conditions found with relapsed/refractory multiple myeloma. STAb-T recruited activity at extremely low effector-to-target ratios were resistant to inhibition mediated by soluble BCMA released from surface, resulting enhanced cytotoxic responses prevention immune escape vitro. These led robust expansion persistence vivo, generating long-lived memory BCMA-specific could control progression xenograft models, outperforming traditional CAR-T cells. results encourage testing BCMA-STAb-T approach

Language: Английский

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Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(7), P. 643 - 661

Published: May 24, 2024

Abstract By binding to multiple antigens simultaneously, multispecific antibodies are expected substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass constructs, consist engineered structures designed bridge immune effector cells their target, thereby redirecting response toward tumor or infected cells. The increasing number recent clinical trials evaluating engagers reflects important role these molecules in new therapeutic approaches for cancer infections. In this review, we discuss how different types (T natural killer lymphocytes, as well myeloid cells) can be bound by immunotherapy infectious diseases. Furthermore, explore preclinical advancements challenges translating current knowledge from virology field. Finally, speculate on promising future directions that may take treatment antiviral therapy.

Language: Английский

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Sequential immunotherapy: towards cures for autoimmunity

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(7), P. 501 - 524

Published: June 5, 2024

Language: Английский

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Disrupting B and T-cell collaboration in autoimmune disease: T-cell engagers versus CAR T-cell therapy?

Clinical & Experimental Immunology, Journal Year: 2024, Volume and Issue: 217(1), P. 15 - 30

Published: April 20, 2024

B and T cells collaborate to drive autoimmune disease (AID). Historically, B- T-cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, dapirolizumab with variable impact on B-cell depletion (BCD), whereas the majority of patients AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, organ transplantation benefit from BCD anti-CD20 monoclonal antibodies rituximab, ocrelizumab, or ofatumumab. Refractory is a significant problem for incomplete greater frequency IgD-CD27+ switched memory cells, CD19+CD20- plasma that are not directly by antibodies, most lymphoid tissue express CD19. Furthermore, B-T-cell collaboration predominant in tissues at sites inflammation joint kidney, where may be inefficient, due limited access key effector cells. In treatment cancer, chimeric antigen receptor (CAR) therapy engagers (TCE) recruit induce cytotoxicity have delivered promising results anti-CD19 CAR therapies, CD19 TCE blinatumomab CD20 mosunetuzumab, glofitamab, epcoritamab. Limited evidence suggests effective managing refractory we await evaluation use non-oncological indications. Therefore, here, discuss potential mechanistic advantages novel therapies rely disrupt toward overcoming rituximab-resistant AID.

Language: Английский

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Structure and function of therapeutic antibodies approved by the US FDA in 2023

Antibody Therapeutics, Journal Year: 2024, Volume and Issue: 7(2), P. 132 - 156

Published: March 15, 2024

In calendar year 2023, the United States Food and Drug Administration (US FDA) approved a total of 55 new molecular entities, which 12 were in class therapeutic antibodies. Besides antibody protein drugs, US FDA also another five non-antibody making broader drugs about 31% drugs. Among antibodies by FDA, 8 relatively standard IgG formats, 3 bivalent, bispecific 1 was trivalent, antibody. no antibody-drug conjugates, immunocytokines or chimeric antigen receptor-T cells approved. Of antibodies, two targeted programmed cell death receptor-1 (PD-1) for orphan indications, CD20 diffuse large B lymphoma, different receptors (B-cell maturation [BCMA] G-coupled receptor C, group 5, member D [GPRC5D]) treatment multiple myeloma, one each that amyloid-β protofibrils Alzheimer's disease, neonatal Fc alpha-chain myasthenia gravis, complement factor C5 CD55 deficiency with hyper-activation complement, angiopathic thrombosis severe protein-losing enteropathy interleukin (IL)-23p19 severely active ulcerative colitis, IL-17A-F plaque psoriasis respiratory syncytial virus (RSV)-F season-long RSV prophylaxis infants.

Language: Английский

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Tri-specific tribodies targeting 5T4, CD3, and immune checkpoint drive stronger functional T-cell responses than combinations of antibody therapeutics

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 10, 2025

Abstract One of the most promising cancer immunotherapies is based on bi-specific T-cell engagers (BiTEs) that simultaneously bind with one arm to a tumor-associated antigen tumor cells and other CD3 complex T form TCR-MHC independent immune synapse. We previously generated four novel tri-specific tribodies made up Fab targeting 5T4, an oncofetal expressed several types tumors, scFv cells, additional specific for checkpoint (IC), such as PD-1, PD-L1 or LAG-3. To verify their advantages over combinations BiTEs (CD3/TAA) IC inhibitors, recently used overcome immunosuppressive environment, here we tested functional properties in comparison clinically validated mAbs same ICs, alone combination control devoid immunomodulatory scFvs, called 53 P. found activated human peripheral blood mononuclear more efficiently than (atezolizumab, pembrolizumab, relatlimab) either P, leading stronger cytotoxicity cytokines release. In particular, 53L10 tribody displayed much potent effects P all led complete regression vivo, showing higher efficacy atezolizumab. shed light molecular basis this potentiated anti-tumor activity by evidencing insertion anti-PD-L1 moiety not only binding but also blocked increased induced IFNγ secretion due activation. These results are important design antigens.

Language: Английский

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Immune Cell Engagers: Advancing Precision Immunotherapy for Cancer Treatment

Antibodies, Journal Year: 2025, Volume and Issue: 14(1), P. 16 - 16

Published: Feb. 11, 2025

Immune cell engagers (ICEs) are an emerging class of immunotherapies designed to harness the immune system's anti-tumor potential through precise targeting and activation effector cells. By engaging T cells, natural killer (NK) phagocytes, ICEs overcome challenges such as evasion MHC downregulation, addressing critical barriers in cancer treatment. T-cell (TCEs), led by bispecific (BiTEs), dominate field, with innovations half-life-extended BiTEs, trispecific antibodies, checkpoint inhibitory driving their application hematologic solid malignancies. NK (NKCEs) phagocyte (PCEs) rapidly progressing, drawing on cells' innate cytotoxicity macrophages' phagocytic abilities target tumors, particularly immunosuppressive microenvironments. Since FDA approval Blinatumomab 2014, have transformed oncology landscape, nine FDA-approved products numerous candidates clinical trials. Despite toxicity, resistance, limited efficacy ongoing research into advanced platforms combination therapies highlights growing provide personalized, scalable, effective treatments. This review investigates mechanisms, platforms, trends, progress ICEs, emphasizing pivotal role advancing precision immunotherapy promise a cornerstone next-generation therapies.

Language: Английский

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