Chitosan-Based Materials and Strategies in Immunotherapy and Synergistic Immunochemotherapy: A Focus on Gene-Based Immunoregulation and Car-T and Adoptive Cell Transfer Publisher



S Safarzadeh SAJAD ; Sm Naghib Seyed MORTEZA ; G Takdehghan GHASEM
Source: Carbohydrate Polymer Technologies and Applications Published:2025

Abstract

Cancer immunotherapy, which utilizes the body's immune system components to target and eliminate malignancies, has emerged as a cornerstone of modern therapeutic approaches. Despite significant advancements, persistent challenges related to therapeutic efficacy, safety profiles, and precise delivery remain critical barriers. Chitosan (CS), a naturally derived polysaccharide distinguished by its biodegradability, biocompatibility, non-immunogenicity, and non-toxicity, has garnered considerable attention as a promising solution to overcome these hurdles. CS-based delivery platforms significantly enhance therapeutic bioavailability, facilitate targeted modulation of immune responses, and potentiate robust antitumor activity. Moreover, the inherent versatility of CS enables the development of tailored, responsive, and multifunctional delivery systems, amplifying the effectiveness of cancer immunotherapy. This review evaluates recent advances in CS-integrated cancer immunotherapeutic strategies. Initially, we examine CS applications in oncolytic viral immunotherapy, emphasizing improved tumor-specific targeting, efficient viral delivery, and enhanced immune activation. Subsequently, we assess CS-based adjuvants and vaccines in strengthening antigen-specific immune responses. Furthermore, we discuss nucleic acid-based immunotherapy employing CS carriers, focusing particularly on their ability to activate critical immune signaling pathways, notably the cGAS–STING axis, enhancing systemic antitumor immunity. Additionally, the potential role of CS in optimizing adoptive cell therapies, including CAR-T cell treatments, is explored, underscoring improvements in cellular trafficking, persistence, and therapeutic outcomes. Finally, we analyze the integration of CS-enhanced immunotherapy with complementary modalities such as chemotherapy, phototherapy, radiotherapy (RT), sonodynamic therapy (SDT), metabolic therapy, and microwave thermotherapy, highlighting their collective potential as powerful combinational strategies for comprehensive tumor eradication. © 2025 Elsevier B.V., All rights reserved.