Recent progress of vaccines administration via microneedles for cancer immunotherapy

Therapeutic cancer vaccines have undergone a resurgence in the past decade. Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis, percutaneous vaccination is considered to be an ideal treatment route. For convenient administration, the recent development of microneedles (MNs) provides a safe, painless, and low-cost transdermal delivery strategy, which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability. However, the therapeutic effect of MNs-based cancer vaccines is not optimal, which is limited by the complex set of host, tumor, and environmental factors, as well as the limited vaccine loading capacity. Therefore, further improvements are still required to push their clinical translation. In this critical review, we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy, summarize the recent advances in MNs-based cancer vaccination, and provide an overview of various design strategies and mechanisms for active or passive targeting delivery, aiming to develop safer, more effective, and more stable MNs-based cancer vaccines. Finally, we briefly describe the potential of vaccine platforms in combination with other therapies, suggest the need to design vaccines according to specific circumstances, and discuss the biosafety of repeated administration for enhancing clinical efficacy.