Novel Immunotherapy Targeting Local and Systemic Immunity for Treatment of Ocular Surface Squamous Neoplasia

Project Summary Ocular surface squamous neoplasia (OSSN) is a progressive ocular cancer that lacks approved treatments and is increasing in prevalence globally. We have developed a new liposomal-TLR agonist immunotherapy (LTAC) that in a novel equine spontaneous OSSN model effectively induces OSSN resolution following topical and perilesional administration in most treated animals. We now propose to use the equine OSSN model to elucidate immunological mechanisms underlying the antitumor activity of LTAC immunotherapy. In Aim 1, local immune responses will be investigated using tumor biopsy and corneal swab samples, including immunohistochemistry and transcriptomic analysis. These studies will identify immune correlates with responsiveness and resistance to immunotherapy. In Aim 2 we will determine whether LTAC immunotherapy also induces systemic immunity to OSSN, using OSSN antigen-specific T cell and antibody assays. These studies overall will advance the field of ocular immunotherapy for ocular cancers and provide important new insights into local and systemic OSSN immunity.