Nano-immunotherapy: Unique mechanisms of nanomaterials in synergizing cancer immunotherapy

Abstract Therapeutic targeting of the immune system, including chimeric antigen receptor-T cell therapy, immune checkpoint blockade therapy, neoantigen vaccines, and small molecule modulators emerges as one of the most effective therapeutic modalities for treating various cancers in human patients. However, clinical efficacies of these immunotherapeutics are generally modest and only a minority of cancer patients benefit from immunotherapy. Further, broad adverse effects, lack of reliable biomarkers, tumour relapses, drug resistance, and metastasis have become increasingly recognized concerns, which may restrain their clinical utility. Unlike most other anticancer strategies, nanomaterial-based therapeutics parade unique and distinct biological features to achieve precision targeting, local drug release, and enhancing therapeutic efficacy. As long-term and sustained release of immunotherapeutics are necessary for enhancing anticancer immunity, nanotechnology ensures accumulation of immunotherapuetics, controlled release, and precision delivery of immune drugs. Combination of these two therapeutic modalities would provide synergistic efficacy for effectively treating various cancers in human patients. To the best of our knowledge, the concept of combination therapy employing nanomaterials and immunotherapy has been overlooked. In this article, we discuss possible mechanisms underlying nano-immunotherapy and unique opportunities of nanotechnology in synergizing cancer treatment.