Monoclonal antibodies have revolutionized cancer treatment over the past several decades, significantly improving patient outcomes through targeted mechanisms and reduced off-target toxicity. Traditional therapeutic antibodies, including those targeting tumor antigens and immune checkpoint inhibitors, have become cornerstone treatments for various malignancies, demonstrating significant clinical efficacy in both hematologic cancers and solid tumors. However, therapeutic challenges remain, including limited efficacy in solid tumors, acquired resistance, and immunological escape. To overcome these obstacles, antibody engineering has emerged as a pivotal approach, enhancing the therapeutic potential of antibodies through techniques such as Fc modification for improved immune effector function, affinity maturation, and the development of novel antibody formats.

Building further upon these advances, the emerging AntibodyPlus paradigm integrates antibodies with additional functional components, such as drugs, nucleic acids, cytokines, enzymes, nanoparticles, or engineered immune cells. These innovative multi-component therapeutics offer the potential to enhance specificity, boost anti-tumor efficacy, mitigate adverse effects, and overcome resistance mechanisms in cancer therapy. AntibodyPlus therapeutics include a variety of sophisticated formats, notably antibody-drug conjugates (ADCs), bispecific and multispecific antibodies, antibody-cytokine fusion proteins (immunocytokines), antibody-nanoparticle conjugates, antibody-oligonucleotide conjugates (AOCs), antibody-enzyme fusions, and antibody-engineered immune cell conjugates such as CAR-T or CAR-NK cells. By leveraging the specificity of antibodies combined with potent effector modules, these therapeutics can directly modulate the tumor microenvironment, enhance immune surveillance, and deliver targeted cytotoxicity to cancer cells. The field of AntibodyPlus therapeutics is rapidly evolving with significant advancements in clinical development. Recent FDA approvals and promising clinical trials underscore the potential of these therapies. Nevertheless, challenges such as payload stability, linker design, immunogenicity, optimal dosing strategies, patient stratification, and regulatory considerations remain critical topics requiring further exploration and innovation.

This Research Topic aims to provide a comprehensive overview of recent advancements, mechanistic insights, clinical progress, and future opportunities for antibody engineering innovations and AntibodyPlus therapeutics in oncology. Contributions should focus on innovative strategies and technologies for optimizing design and therapeutic efficacy, as well as detailed mechanistic investigations that reveal interactions with tumor biology and immune modulation. Additionally, reports of in-depth clinical experiences with emerging antibody platforms are encouraged.

We welcome submissions that explore, but are not limited to, the following themes:
• Advances in antibody engineering techniques, including Fv engineering, Fc engineering, and novel antibody formats.
• Mechanistic studies on AntibodyPlus therapeutics and their impact on tumor signaling pathways.
• Development and optimization of antibody-drug conjugates and antibody-oligonucleotide conjugates.
• Innovations in bispecific and multispecific antibodies for simultaneous modulation of multiple tumor-associated targets.
• Antibody-engineered immune cell therapies (CAR-T, CAR-NK cells) and their clinical efficacy in solid tumors.
• Strategies for enhancing tumor penetration and payload release in AntibodyPlus constructs.
• Immunogenicity and safety profiling of AntibodyPlus therapeutics in preclinical and clinical settings.
• Novel payloads and linkers designed for improved specificity and reduced systemic toxicity.
• Clinical trial results, case studies, and therapeutic outcomes of AntibodyPlus-based therapies.
• Biomarkers and patient stratification approaches to optimize therapeutic outcomes and personalize treatment.
• Regulatory and manufacturing considerations for next-generation AntibodyPlus therapies.
• Clinical outcomes and mechanistic insights into traditional therapeutic antibodies in cancer therapy.

Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

Topic Editor Heyu Chen is employed by AstraZeneca. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

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AntibodyPlus Therapeutics in Oncology: Innovative Mechanisms, Therapeutic Strategies, and Clinical Advances