Abstract 6754: A microneedle array patch chemo-immunotherapy for cutaneous squamous cell carcinoma

Abstract

Abstract Cutaneous squamous cell carcinoma (cSCC) is the second most common human malignancy worldwide. Current therapies, including surgical excision, are associated with significant morbidities and considerable expense. Multiple efforts are now underway to develop novel therapies that are effective, durable, safe, cost-effective, and patient-friendly. Here, we report ongoing efforts to develop a localized dissolvable microneedle array patch (MAP) based therapy for cSCC. Our approach is based on the hypothesis that the delivery of an immunogenic cell death (ICD) inducing chemotherapeutic agent to the tumor microenvironment (TME) of accessible cSCCs could kill tumor cells as a source of antigen and induce a proinflammatory TME to generate a potent patient-specific anti-tumor immune response. Specifically, we evaluated MAP therapy using a UV-induced preclinical cSCC mouse model. We applied MAPs delivering the potent ICD-inducing chemotherapeutic agent, doxorubicin (DOX) to UV-induced tumors. MAPs efficiently delivered DOX to the tumor microenvironment. Compared to traditional needle injection, MAP delivery resulted in sustained high levels of DOX in the TME with minimally systemic exposure. Cell death was evident in MAP-DOX-treated tumors, and treatment resulted in tumor regression, increased survival, and long-term immune protection. Further, we found that tumor regression was associated with an early proinflammatory neutrophilic infiltrate. Taken together, our results suggest that MAP delivery of doxorubicin may be a promising approach to cSCC treatment. and that proinflammatory neutrophils are likely an important component of the early infiltrate that leads to tumor regression. Citation Format: Yufan Yang, Haotong Zhang, Cara D. Carey, Jiying Zhang, Stephen C. Balmert, Emrullah Korkmaz, Louis D. Falo. A microneedle array patch chemo-immunotherapy for cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6754.