From preclinical platforms to clinical translation: advancing combination immunotherapy discovery

Recent advances in biomedical technologies—including microphysiological systems (MPS), humanized and chimeric animal models, nanomaterials, cell-based therapies, and AI-powered biostatistical analysis—have fundamentally reshaped the landscape of cancer research and immunotherapeutic development. We are at a singularity in immunotherapy—a transformative moment driven by the integration of biomedical techniques and AI-enabled analytics. Together, these innovations enable rapid screening and optimization of personalized treatments, whether mRNA-based therapeutics, stem cell–derived products, or nano-enabled formulations. Modern preclinical verification platforms increasingly recapitulate human physiology, enhancing translational predictability and accelerating therapeutic discovery.Importantly, the immune system serves as a central crossroads for these technologies and interventions. Acting as both mediator and amplifier of therapeutic effects, immunity integrates diverse treatment modalities within a unified biological framework. With the support of immune responses, the effects of newly developed medications or nanomaterials can become more powerful and more individualized for each patient. Because immune responses are highly individualized, advanced preclinical platforms provide an essential foundation for discovering and refining patient-specific combination immunotherapies with greater precision and efficiency.The central problem in combination immunotherapy discovery is not simply identifying multiple active agents, but determining how to combine them in a rational, coordinated, and mechanistically meaningful way. Unstructured integration of new technologies with classical signaling pathway approaches may create biological redundancy, excessive immune activation, or therapeutic unpredictability. Therefore, this Research Topic aims to redefine combination strategies by positioning the immune system as the critical breakthrough point and organizing principle.Rather than mixing modalities arbitrarily, we propose leveraging immune response dynamics as the core framework for therapeutic design. By utilizing advanced preclinical platforms—such as physiologically relevant modeling systems, humanized biological models, and AI-driven analytical tools—combinations can be evaluated based on immune activation strength, modulation balance, and patient-specific immune signatures. Recent advances in functional profiling and predictive modeling enable systematic optimization of synergy, sequencing, and dosing.Through an immunity-centered strategy, combination therapies can be developed as coordinated and amplified interventions, enhancing therapeutic precision while minimizing unintended immune chaos.I. Advanced Preclinical Modeling and Platform DevelopmentThis section focuses on preclinical research leveraging advanced biological models and analytical technologies, including microphysiological systems (MPS) such as organoids, organ-on-chip platforms, and microfluidic systems; humanized and chimeric animal models; nanomaterial-based therapeutic platforms; cell-based immunomodulatory systems; and AI-powered biostatistical and predictive analysis frameworks. Emphasis is placed on the development and optimization of innovative delivery systems and engineered immunomodulatory strategies within physiologically relevant models, as well as mechanistic evaluation of immune activation, modulation, and combinational synergy in structured preclinical environments.II. Mechanistic and Target Discovery for Precision ImmunotherapyThis section highlights the identification and validation of novel targets within innate and adaptive immune pathways using advanced modeling systems. It includes preclinical investigations of personalized immunotherapy strategies guided by immune profiling and data-driven modeling, along with functional characterization of immune–tumor interactions to inform rational and mechanism-based combination design.III. Translational Bridging and Clinical ValidationThis section addresses translational efforts that connect preclinical discoveries to clinical implementation, including early-phase clinical studies evaluating efficacy, safety, and optimization of emerging or repurposed immunotherapies informed by advanced platforms. It also welcomes systematic reviews, meta-analyses, and case reports that identify translational gaps or present rare and breakthrough immune-targeted therapeutic strategies with clear clinical implications.We welcome original research articles, translational studies, clinical investigations, review articles, systematic reviews, meta-analyses, and impactful case reports, particularly those advancing rational combination strategies and precision immunity-centered approaches.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Xiaolong Wang, TONGZU LIU, Zijian Wang Source: https://www.frontiersin.org/research-topics/78754/from-preclinical-platforms-to-clinical-translation-advancing-combination-immunotherapy-discovery