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 sites. 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 molecules that modulate the TME for improved T cell infiltration, immunomodulators to overcome local immunosuppression, and viral antigen tags to induce antigen presentation. This enables the redirection of specific T cells, creating a platform for universal "off-the-shelf" therapy. This review discusses the application of nanomaterials to augment chimeric antigen receptor T (CAR-T) cell efficacy, harness bystander T cell activity, and reinvigorate 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.