Targeting Aging Hallmarks with Monoclonal Antibodies: A New Era in Cancer Immunotherapy and Geriatric Medicine

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(11), P. 4982 - 4982

Published: May 22, 2025

Aging is characterized by a progressive deterioration in physiological function and an increased susceptibility to age-related diseases, such as cancer. Monoclonal antibodies (mAbs) constitute novel therapeutic approach aimed at addressing aging mechanisms cellular senescence, inflammaging, immunosenescence. This text presents overview of mAb methods the markers their potential application cancer treatment. The mAbs can be categorized into senolytics, senescence-associated secretory phenotype (SASP) neutralizers, immune checkpoint inhibitors, each targeting fewer aging-related pathways relevant enhancement than last. Translating promising preclinical evidence enhanced efficacy safety therapy challenges, particularly older populations. study examines treatment disorders, focusing on current future roles oncology practice.

Language: Английский

LlamaAffinity: A Predictive Antibody Antigen Binding Model Integrating Antibody Sequences with Llama3 Backbone Architecture

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 28, 2025

Abstract Antibody-facilitated immune responses are central to the body’s defense against pathogens, viruses, and other foreign invaders. The ability of antibodies specifically bind neutralize antigens is vital for maintaining immunity. Over past few decades, bioengineering advancements have significantly accelerated therapeutic antibody development. These antibody-derived drugs shown remarkable efficacy, particularly in treating Cancer, SARS-Cov-2, autoimmune disorders, infectious diseases. Traditionally, experimental methods affinity measurement been time-consuming expensive. With realm Artificial Intelligence, silico medicine has revolutionized; recent developments machine learning, use large language models (LLMs) representing antibodies, opened up new avenues AI-based designing improving prediction. Herein, we present an advanced antibody-antigen binding prediction model (LlamaAffinity), leveraging open-source Llama 3 backbone sequence data employed from Observed Antibody Space (OAS) database. proposed approach improved over existing state-of-the-art (SOTA) approaches (AntiFormer, AntiBERTa, AntiBERTy) across multiple evaluation metrics. Specifically, achieved accuracy 0.9640, F1-score 0.9643, a precision 0.9702, recall 0.9586, AUC-ROC 0.9936. Moreover, this strategy unveiled higher computational efficiency, with five-fold average cumulative training time only 0.46 hours, lower than previous studies. LlamaAffinity defines benchmark prediction, achieving performance immunotherapies immunoinformatics field. Furthermore, it can effectively assess affinities following novel design, accelerating discovery optimization candidates.

Language: Английский

Assessment of biophysical properties of the first-in-class anti-cancer IgE antibody drug MOv18 IgE demonstrates monomeric purity and stability

mAbs, Journal Year: 2025, Volume and Issue: 17(1)

Published: May 28, 2025

Therapeutic monoclonal antibodies, which are almost exclusively IgG isotypes, show significant promise but prone to poor solution stability, including aggregation and elevated viscosity at dose-relevant concentrations. Recombinant IgE antibodies emerging cancer immunotherapies. The first-in-class MOv18 IgE, recognizing the cancer-associated antigen folate receptor-alpha (FRα), completed a Phase 1 clinical trial in patients with solid tumors, showing early signs of efficacy low dose. inaugural process development scaled manufacture for testing were undertaken little baseline knowledge about phase behavior recombinant We evaluated physical stability response environmental formulation stresses encountered throughout shelf life. analyzed changes using multiple orthogonal analytical techniques, particle tracking analysis, size exclusion chromatography, multidetector flow field fractionation hyphenated UV. used dynamic multiangle light scattering profile status. Formulation pH 6.5, selected use trial, resulted high monomeric purity no submicron proteinaceous particulates. 5.5 7.5 induced sub-visible formation. was resistant freeze-thaw stress, retaining purity. Exposure thermal stress temperatures loss aggregation. Agitation stress-induced subvisible aggregation, not significantly affected. retains conditions, confirming stability. Our results offer crucial guidance future IgE-based drug development.

Language: Английский