Innovations in adoptive cell therapy: Overcoming safety and efficacy barriers through engineering, vaccination, and TME remodeling

Adoptive cell therapy (ACT) has emerged as a transformative approach in cancer immunotherapy, with remarkable clinical success in hematological malignancies. However, its broader application, particularly in solid tumors, remains limited by critical challenges related to safety, efficacy, persistence, and tumor immune evasion. These barriers highlight the urgent need for innovative strategies that enhance the therapeutic index of ACT while minimizing toxicity.Recent advances in cellular engineering, including next-generation CAR-T and CAR-NK cells, gene editing technologies, and synthetic biology approaches, are redefining the potential of adoptive cell therapies. In parallel, cancer vaccination strategies, ranging from neoantigen-based vaccines to oncolytic and dendritic cell vaccines, are increasingly explored as complementary tools to improve ACT priming, expansion, and long-term functionality. Moreover, growing insights into the tumor microenvironment (TME) have underscored its pivotal role in shaping ACT efficacy, resistance mechanisms, and immune-related adverse events.This Research Topic aims to bring together original research, reviews, and perspectives that explore innovative approaches to overcome safety and efficacy barriers in adoptive cell therapy. Contributions addressing cellular engineering, combinatorial strategies with vaccines, and modulation of the tumor microenvironment are particularly encouraged. By integrating mechanistic insights with translational and clinical perspectives, this Topic seeks to provide a comprehensive overview of emerging solutions to optimize ACT performance across cancer settings.We welcome submissions covering, but not limited to, the following themes:• Engineering strategies to enhance safety, specificity, and persistence of CAR-T and CAR-NK cells• Mechanisms of toxicity and approaches to mitigate on-target/off-tumor effects and cytokine-related adverse events• Combination of adoptive cell therapies with cancer vaccines or immune priming strategies• Tumor microenvironment remodeling to improve ACT infiltration, function, and durability• Overcoming immune suppression, antigen escape, and resistance to ACT• Translational and clinical advances in next-generation adoptive cell therapiesThis Research Topic aims to foster interdisciplinary discussion and accelerate the development of safer and more effective adoptive cell therapy strategies for cancer patients. Topic editors: Gaia Zuccolotto, Enzo Medico Source: https://www.frontiersin.org/research-topics/78782/innovations-in-adoptive-cell-therapy-overcoming-safety-and-efficacy-barriers-through-engineering-vaccination-and-tme-remodeling