Advances in nanotechnology-augmented T cell-based novel cancer immunotherapies

Malignant tumors are a leading global cause of death, motivating advances in treatment strategies. Conventional immunotherapies, including checkpoint inhibitors, vaccines, and cytokine therapies are limited by low response rates, toxicity, or target specificity. Novel immunotherapies harness the patient’s T cells through genetic or redirection strategies but also encounter tumor microenvironment (TME) suppression, inefficient antigen presentation, and T cell exhaustion. Nanotechnology offers tailored solutions. Nanocarriers deliver enzymes to improve T cell infiltration, immunomodulators to counteract TME suppression, and viral antigen tags (e.g., SARS-CoV-2 Spike) to force antigen presentation, enabling redirection of pre-existing virus-specific T cells for "off-the-shelf" therapy. In this review, we discuss nanomaterial applications to improve Chimeric Antigen Receptor T Cell (CAR-T) function, bystander T cell cytotoxicity, and pre-existing immunity. Key strategies include immune synapse modulation, barrier penetration, reducing T cell exhaustion, and sustaining long-term efficacy. Challenges in scalability, safety, and patient variability remain, urging development of smart nanosystems, personalized vaccines, and combination therapies. Nanotechnology promises to overcome current immunotherapy limitations and redefine cancer treatment paradigms toward potent, broad-spectrum, and durable tumor eradication.