Aug 2026· Biochimica et biophysica acta. Reviews on cancer· Vol 1881, pp.
189685
· 0 citations· 110 references
Medicine
TL;DR
This review article focuses on CAR-T cell bioengineering, antitumor mechanism of action, challenges and limitations, as well as the latest innovative nanotechnological solutions for complementing CAR-T cell immunotherapy.
Abstract
Chimeric antigen receptor (CAR)-T cell immunotherapy is one of the emerging advancements in personalized treatment of cancer, whose design is based on the genetic modification of T cells to express chimeric antigen receptors (CARs) to generate CAR-T cells, specifically targeting cancer tissues. Despite the fact that immunotherapy provides significant antitumor activity, only a limited number of therapies reached the market after their FDA approval because of the accompanying challenges including tumor resistance, side effects, high cost of production, possible toxicities during CAR-T cells engineering, and poor selectivity. Nanotechnology has emerged as a promising approach for improving drug targeting, selectivity and reducing their side effects. In this context, recent advances highlight the innovative integration of nanomaterials for enhancing CAR-T cell engineering, delivery, and in vivo functionality. Nanotechnology-enabled strategies such as nanoparticle-based gene delivery systems, nanoformulations for controlled CAR expression, and tumor microenvironment modulation have demonstrated significant potential in overcoming current therapeutic limitations. Therefore, substantial research efforts are currently focused on integrating this technology in developing CAR-T cell immunotherapy. This review article focuses on CAR-T cell bioengineering, antitumor mechanism of action, challenges and limitations, as well as the latest innovative nanotechnological solutions for complementing CAR-T cell immunotherapy. It also emphasizes the translational applications and design innovations of nanotechnology, including precision targeting platforms and multifunctional nanocarriers, highlighting that nanotechnology may play an important role in advancing the efficacy, safety, and clinical applicability of personalized CAR-T cancer immunotherapy.
This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy and highlights synergistic effects achieved by combining nanoparticles with other treatments like chemotherapy, radiation, photothermal/photodynamic therapy, and more, which can turn hard-to-treat tumors into susceptible targets.
U. Cho, Jing-Jing Pu, Amit Sharma et al.· Molecular Cancer· 0 citations
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of several hematological malignancies, but its broader application remains constrained by the complexity, cost, and time required for conventional ex vivo manufacturing.
In vivo
CAR T-cell therapy has emerged as a promising next-generation strategy that aims to generate CAR T cells directly within the patient through targeted delivery of CAR-encoding genetic information to endogenous T cells. This approach has the potential to simplify treatment workflows, shorten manufacturing timelines, reduce production costs, and improve the accessibility of CAR-based immunotherapy. In this review, we summarize the conceptual evolution from ex vivo to
in vivo
CAR T-cell therapy and discuss major delivery platforms for
in vivo
CAR T-cell generation, including engineered lentiviral vectors (LVs), adeno-associated viral vectors, lipid nanoparticles, polymeric nanoparticles, extracellular vesicles, and fusogenic nanovesicles. We further examine key translational challenges and corresponding optimization strategies, including approaches to improve T-cell targeting specificity and delivery controllability, reduce vector immunogenicity, enhance CAR expression persistence, mitigate safety concerns associated with ectopic transduction or genomic integration, and potentially overcome the physical, antigenic, and immunosuppressive barriers encountered in solid tumors. Finally, we summarize early clinical trial progress and discuss future directions for improving the safety, efficacy, and translational potential of
in vivo
CAR T-cell therapy. Overall,
in vivo
CAR T-cell therapy represents an important extension of adoptive cell therapy and may reshape the development and clinical implementation of cell-based immunotherapies.
The biological mechanisms underlying resistance to CAR-T therapy in solid tumors are examined and emerging combination strategies designed to enhance tumor recognition, trafficking, persistence, and antitumor activity are critically evaluated.
Wei Cheng, Mei-Lan Liu, Yu-Hua Diao et al.· Cancer Biome and Targeted Th...· 0 citations
Abstract Malignant tumors remain one of the most serious challenges to global health. Although chemotherapy and targeted therapy are available treatment options, their effectiveness is often limited by the complexity of the tumor microenvironment (TME). In recent years, immunotherapy has demonstrated significant potential in harnessing the immune system to combat cancer. Polymeric nanoparticles (PNPs) have emerged as versatile platforms for cancer immunotherapy, offering favorable biocompatibility, tunable size, and surface functionalization for targeted delivery. In this review, we critically evaluate PNP design strategies, emphasizing stimuli-responsive release mechanisms that enable spatiotemporally controlled drug delivery within the TME, thereby enhancing efficacy and minimizing systemic toxicity. We further highlight PNP-enabled synergistic therapies, including photodynamic, chemodynamic, and sonodynamic therapies, that induce immunogenic cell death (ICD) and potentiate antitumor immunity, as well as PNP-based vaccines (RNA, peptide, and in situ) that activate dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs). Nevertheless, the clinical translation of PNP-based therapies is constrained by multiple factors, including manufacturing scalability, emulsifier-related toxicity, rapid RES clearance, inherent immunogenicity, and the heterogeneity of the TME. By bridging material engineering with immunological barriers and translational challenges, this review provides a critical framework for designing next-generation PNP immunotherapies toward personalized cancer treatment.
Dong-Qi Li, Jia Hu, Ying-Shu Cui et al.· International Journal of Nan...· 0 citations
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of hematologic malignancies but has demonstrated limited efficacy in solid tumors, mainly due to the complex and immunosuppressive tumor microenvironment (TME). Among the strategies to overcome this challenge, targeting the tumor stroma rather than the tumor cells themselves has gained increasing interest. In this context, fibroblast activation protein alpha (FAP), a cell surface protease overexpressed by cancer-associated fibroblasts, represents a promising target. With the aim of remodeling the TME, enhancing immune infiltration, and suppressing tumor growth, numerous FAP-directed CAR T-cell therapies have been developed in the last decade, leading to the clinical translation of two candidates. To improve the flexibility and safety profile of CAR T-cell therapies, several groups have designed more controllable and modular approaches, including adapter CAR T-cell systems, which enable on-demand activation of effector cells through the administration of an adapter molecule. In parallel, the development of FAP-targeted radiotracers, particularly FAP inhibitors (FAPIs), has enabled high-contrast imaging of solid tumors and introduced attractive opportunities for radioligand therapy. The convergence of these advances has given rise to immunotheranostic strategies that integrate CAR T-cell immunotherapy and radioligand delivery within a unified framework. This review traces the evolution of FAP-directed CAR T-cell strategies, from conventional designs to adapter-based and theranostic platforms, and examines how modular adapters bring immunotherapy and radioligand delivery together within a single immunotheranostic framework, across preclinical and clinical settings.
Hugo Boutier, A. Feldmann, Michael Bachmann· International Journal of Mol...· 0 citations
Nonviral NPs are poised to redefine CAR therapy by enabling scalable, off-the-shelf immune interventions for cancer, autoimmune, and fibrotic diseases.
Ke Huang, Hao Wang, Tao Zhu et al.· Biomaterials· 1 citation
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