Methods in cell biology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Dec. 1, 2023
Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with distinct epitopes, are tremendous concern immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from medical standpoint since most diseases complex, involving several receptors, ligands, signaling pathways. Several research look into processes BsAbs identify different targets such angiogenesis, reproduction, metastasis, regulation. By rerouting cells altering other pathways, proteins perform effector activities addition those natural antibodies. This opens up wide range clinical applications helps patients resistant tumors respond better medication. Yet, further study necessary best conditions where use these medications for treating tumor, their appropriate combination partners, methods reduce toxicity. In this review, we provide insights BsAb format classification based on composition symmetry, as well delivery mode, focus action mechanism molecule, discuss challenges future perspectives development.
Language: Английский
Citations
15
Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216760 - 216760
Published: Feb. 29, 2024
Language: Английский
Citations
6
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8888 - 8888
Published: Aug. 15, 2024
RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability targeting sequences. Nevertheless, shows instability has short half-life in physiological environments such as bloodstream presence RNAase. Therefore, developing reliable delivery strategies important disease sites maximizing therapeutic effect drugs, particularly field immunotherapy. In this mini-review, we highlight two major approaches: (1) vehicles (2) chemical modifications. Recent advances employ nanotechnologies lipid-based nanoparticles, viral vectors, inorganic nanocarriers to precisely target specific cell types facilitate cellular entry. On other hand, modification utilizes alteration structures via addition covalent bonds N-acetylgalactosamine or antibodies (antibody-oligonucleotide conjugates) receptors cells. The pros cons these technologies are enlisted review. We aim review acid their systems, strategies, related Finally, express our perspective on potential combination RNA-based click chemistry with adoptive therapy (e.g., B cells T cells) address issues duration associated antibody-oligonucleotide conjugate drugs.
Language: Английский
Citations
6
Advanced Science, Journal Year: 2024, Volume and Issue: 11(41)
Published: Sept. 5, 2024
Abstract Immunotherapy targeting immune checkpoints (ICPs), such as programmed death‐ligand‐1 (PD‐L1), is used a treatment option for advanced or metastatic non‐small cell lung cancer (NSCLC). However, overall response rate to anti‐PD‐L1 limited due antigen heterogeneity and the immune‐suppressive tumor microenvironment. Human leukocyte antigen‐G (HLA‐G), an ICP well neoexpressed tumor‐associated antigen, previously demonstrated be beneficial target in combination with anti‐PD‐L1. In this study, nanobody‐based trispecific T engager (Nb‐TriTE) developed, capable of simultaneously binding cells, macrophages, cells while redirecting toward expressing PD‐L1‐ and/or HLA‐G. Nb‐TriTE shows broad spectrum anti‐tumor effects vitro by augmenting cytotoxicity mediated human peripheral blood mononuclear (PBMCs). humanized immunodeficient murine NSCLC model, exhibits superior anti‐cancer potency compared monoclonal antibodies bispecific engagers. Nb‐TriTE, at dose pharmacoactivity, does not induce additional enhancement circulating cytokines secretion from PMBCs. effectively prolongs survival mice without obvious adverse events. conclusion, study introduces innovative therapeutic approach address challenges immunotherapy microenvironment through utilizing dual ICP‐targeting Nb‐TriTE.
Language: Английский
Citations
6
Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)
Published: Oct. 29, 2024
Abstract Natural killer cell engagers (NKCEs) are a specialised subset of antibodies capable simultaneously targeting endogenous NK cells and tumour cells, generating precise effective cytolytic responses against cancer. This review systematically explores as rising star in NK‐mediated immunotherapy, specifically focusing on multi‐specific engagers. It examines the diverse configuration NKCEs how certain biologics could be employed to boost activity, including activating receptor engagement cytokine incorporation. Some challenges future perspectives current therapy also discussed, optimising pharmacokinetics, addressing immunosuppressive microenvironment exploring potential combinatorial approaches. By offering an in‐depth analysis landscape trajectories cancer treatment, this serves valuable resource for understanding promising field immunotherapy. Highlights Innovative : represent new class immunotherapeutics tumours by cells. Multi‐specific formats The transition from bi‐specific enhances their versatility therapeutic efficacy. Mechanisms action have improve activation engaging receptors incorporating cytokines. Clinical Current clinical trials demonstrate safety efficacy various across different types. Future research directions Optimising NKCE designs combination therapies essential overcoming treatment.
Language: Английский
Citations
6
European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(8)
Published: May 28, 2024
Abstract In the last decade, there has been a surge in developing immunotherapies to enhance immune system's ability eliminate tumor cells. Bispecific antibodies known as T cell engagers (TCEs) present an attractive strategy this pursuit. TCEs aim guide cytotoxic cells toward cells, thereby inducing strong activation and subsequent lysis. study, we investigated activity of different on both conventional alpha‐beta (αβ) unconventional gamma delta (γδ) were built using camelid single‐domain (VHHs) targeting tumor‐associated antigen CEACAM5 (CEA), together with receptor chains or CD3 domain. We show that Vγ9Vδ2 display stronger vitro antitumor than αβ when stimulated CD3xCEA TCE. Furthermore, restricting fresh human peripheral limited production protumor factors proinflammatory cytokines, commonly associated toxicity patients. Taken together, our findings provide further insights γδ cell‐specific hold promise specific, effective, potentially safe molecules improve immunotherapies.
Language: Английский
Citations
5
Immunology Letters, Journal Year: 2024, Volume and Issue: 270, P. 106942 - 106942
Published: Nov. 1, 2024
Language: Английский
Citations
5
Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(8), P. 2444 - 2460
Published: May 31, 2024
Language: Английский
Citations
5
Apmis, Journal Year: 2025, Volume and Issue: 133(1)
Published: Jan. 1, 2025
Development of antibodies for clinical use is a complex process involving numerous aspects, with antigen specificity being the most important. Initially, polyclonal antibodies, that can recognize multiple specific and nonspecific antigens (polyreactive), were developed very effective in treatments. Later on, polyspecificity/polyreactivity these (binding to antigens) raised concerns about therapeutic efficacy because their interactions challenges, such as development immune complexes, batch-to-batch variability. This highlighted need more targeted approaches. It was resolved by marked invention hybridoma technology 1975 which resulted revolution antibody field offering monoclonal monospecific (bind single antigen). However, limited application pathologies sparked paradigm shift, leading resurgence polyspecific form (Polybodies), bind antigens, but specifically. Till today, 14 Polybodies are approved use. fluctuation directing evolution engineered going drive biopharmaceutical sector coming years. Through this write-up, we assert fluctuating nature during how it will be crucial advancing biologics.
Language: Английский
Citations
0
Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 291 - 291
Published: Jan. 17, 2025
Objectives: Developing ex vivo models that replicate immune-tumor interactions with high fidelity is essential for advancing immunotherapy research, as traditional two-dimensional in vitro systems often lack the complexity required to fully represent these interactions. Methods: In this study, we establish a comprehensive 3D redirect lysis (3D-RDL) assay using colorectal cancer spheroids and adult stem cell-derived, healthy human organoids evaluate efficacy safety profile of Cibisatamab, bispecific antibody targeting carcinoembryonic antigens (CEAs) on cells CD3 T cells. This model allows us assess cytotoxic activity immune responses, capturing variations therapeutic response not observable simpler systems. Our integrates live imaging cytotoxicity analyses enable precise, real-time tracking effects CEA-expressing tumor compared Additionally, by standardizing effector-to-target cell ratios each co-culture, reproducible workflow enhances data accuracy comparability across assays. Flow cytometry Granzyme B release profiling further allow characterize activation, revealing distinct activation markers patterns tied Cibisatamab treatment. Results: results show effectively induces death CEA expression while being dose-dependent target, off-tumor binding killing non-cancerous intermediate levels. highlights our model's potential predict clinical outcomes, complex responses like selectivity, resistance mechanisms. Conclusions: These findings underscore utility reliable, physiologically relevant tool screening new immunotherapies understanding tumor-immune dynamics.
Language: Английский
Citations
0