A topical chemo-immunotherapy for squamous cell carcinoma.

Abstract We have previously demonstrated that dissolvable microneedle arrays can co-deliver cargos directly to the skin while avoiding systemic distribution. As squamous cell carcinoma (SCC) has a lifetime incidence of 7–11% in the United States and is the second most common non-melanoma skin cancer in persons of white European descent, we sought to determine if MNA delivery of anti-tumor agents induce cell death and improve survival in a mouse model of SCC and in freshly excised human SCCs. To accomplish this, we evaluated the effectiveness of doxorubicin, a chemotherapeutic demonstrated to induce immunogenic cell death, as an MNA delivered therapeutic. Effectiveness was evaluated in mice inoculated with SCC cells and later treated with Blank MNAs (MNA-Blank) or MNAs integrating doxorubicin (MNA-Dox), and in human SCCs treated with MNA-Dox. In mice, MNA-Dox treatment resulted in increased levels of pro-inflammatory cytokine gene expression, increased levels of cell death as determined by TUNEL assays, attenuated tumor growth, and substantially improved survival over MNA-Blank treatment at 20 days post-inoculation (100% survival in MNA-Dox group versus 0% survival in MNA-Blank group). Survival advantage persisted with 40% of MNA-Dox-treated mice alive at 40 days post-inoculation. Similarly, freshly excised human SCCs treated with MNA-Dox demonstrated increased levels of cell death as determined by TUNEL assays. Taken together, these results demonstrate the potential of MNA administration of doxorubicin to effectively induce tumor cell death in a murine model of squamous cell carcinoma and in human SCCs supporting further clinical development.