Recent years have witnessed a rapid expansion of novel therapeutic modalities, including gene editing technologies, engineered cell therapies, RNA-based therapeutics, and advanced protein engineering platforms. These approaches are transforming the treatment landscape across oncology, rare diseases, and chronic conditions. However, their increasing complexity and biological novelty also introduce new challenges related to immune recognition, activation, and tolerance. Both innate and adaptive immune responses can significantly impact therapeutic efficacy, durability, and safety, influencing outcomes such as loss of function, inflammation, or adverse immune-mediated events. At the same time, advances in immunology and bioengineering are providing new tools to better understand and modulate these responses. A comprehensive evaluation of immunogenicity is therefore becoming a central aspect in the development of next-generation therapeutics.
This Research Topic aims to provide a comprehensive and multidisciplinary overview of immune responses to emerging therapeutic modalities, with a particular focus on understanding, predicting, and mitigating immunogenicity. Despite major technological advances, immune-mediated limitations remain a key barrier to the successful translation and broad application of many innovative therapies. These include pre-existing immunity, innate immune sensing of delivery systems, adaptive immune responses to engineered proteins, and immune-driven loss of therapeutic activity.
The goal of this collection is to bring together original research, reviews, and perspectives that address these challenges from both mechanistic and translational perspectives. Contributions exploring novel strategies to reduce immunogenicity—such as protein engineering, immune evasion, transient expression systems, and tolerance induction—are particularly encouraged. Additionally, we aim to highlight advances in immune monitoring, predictive modeling, and safety assessment frameworks that can support the development of safer and more effective therapies. By integrating insights across different platforms, this Research Topic seeks to foster a more unified understanding of immune barriers and opportunities in next-generation therapeutics.
This Research Topic welcomes submissions addressing immune responses and immunogenicity across a wide range of emerging therapeutic platforms.
Topics of interest include, but are not limited to:
• Immune responses to gene editing technologies (e.g., CRISPR/Cas systems, base and prime editing)
• Immunogenicity of engineered proteins and biologics
• Immune interactions with cell therapies (CAR-T, CAR-NK, allogeneic products)
• Innate and adaptive immune responses to RNA therapeutics and delivery systems (e.g., LNPs, viral vectors)
• Mechanisms of immune sensing and activation by novel therapeutic platforms
• Strategies to mitigate immunogenicity (e.g., protein de-immunization, immune cloaking, tolerance induction)
• Immune monitoring and biomarkers of therapeutic response and safety
• Preclinical and clinical assessment of immunogenicity
We welcome Original Research articles, Reviews, Mini-Reviews, Perspectives, and Methods papers.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Curriculum, Instruction, and Pedagogy
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
