As a paradigm shift in cancer treatment, cancer immunotherapy has received tremendous attentions. Instead of directly attacking the tumor, immunotherapeutic agents boost the body’s immune system to kill the cancer cells. Particularly, the immune checkpoint blockade has elicited durable antitumor responses and long-term remissions in a subset of patients. Despite remarkable progress, current methods of checkpoint blockade therapy limit therapeutic benefit in many patients. The largest limitation observed in clinical trials maybe the severity of the adverse effects. Meanwhile, a large fraction of patients failed to respond to these agents. How to enhance immune checkpoints based cancer therapy has become one of the central themes in the field of cancer immunology and immunotherapy. Here we developed a biodegradable microneedle for controlled delivery of immune checkpoint inhibitors toward melanoma. In this study, the microneedle patch was composed of biocompatible hyaluronic acid (HA), which has been widely applied in numerous FDA approved therapeutic formulations. HA is integrated with pH-sensitive dextran nanoparticles that encapsulate immune checkpoint inhibitors such as aPD1 and aCTLA4, and other immunomodulators such as 1-MT. Our strategy based on the biodegradable microneedle for local treatment of melanoma improves the therapeutic efficacy of immune checkpoint inhibitors and can reduce the systemic toxicity simultaneously. This “immune patch” could offer an alternative option for patients with an early stage of melanoma. The patch can prevent primary tumor growth and metastasis before the surgery, if not destroying the primary tumor.

Local delivery of checkpoints antibodies

253rd National Meeting (2017)

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