Effect of in situ immunization with vidutolimod in an oral leukoplakia model
Creators: name: Xu, Yan
Publisher: name: University of Iowa
Year: 2027

description: Leukoplakia is the most common premalignancy in the oral cavity, with the syndrome of white patches or spots forming inside the mouth. The risk factors include chronic irritation such as smoking, alcohol consumption, and chewing betel nuts. The majority of oral squamous cell carcinomas (OSCCs) arise from oral leukoplakia. However, leukoplakia is insufficiently researched and both diagnosing and treating oral leukoplakia are still problematic issues; with diagnosis being highly subjective and treatments (e.g., watchful waiting, conservative drug therapies, and surgical removal) possessing limited efficacy. There are no biomarkers specific for leukoplakia and the diagnosis of leukoplakia highly depends on the pathologist’s analysis of the collected biopsy, which can introduce a lot of variances. Thus, further understanding and an effective therapy for leukoplakia are still highly desirable to lower the risk of recurrence and malignant transformation to oral leukoplakia.
description: Human OSCC and leukoplakia samples were studied histologically and immunologically to reveal the local immune profile. Dendritic cells (DCs) are antigen-presenting cells that are crucial for stimulating CD8+/cytotoxic T cells to perform direct anti-tumor activities. Moderately-differentiated and well-differentiated OSCC were analyzed and compared with adjacent healthy tissue to reveal plasmacytoid DC (pDC) expression and activity. The distribution of a range of immune cells including DCs, CD4+ T cells, CD8+ T cells, macrophages, and B cells in different grades of oral leukoplakia was also investigated through spatial biology analysis.
description: Immune therapy is a promising approach to treating malignancies, however, its effect on the prevention and treatment of premalignancies has been rarely studied. This study focuses on the immune signature of leukoplakia and explores whether stimulating the immune system with an immune adjuvant, vidutolimod, can prevent the progression of oral leukoplakia or even cause disease regression. Vidutolimod comprises a bacteriophage Qβ protein shell encapsulating a Toll-like receptor (TLR)-9 agonist (G10). G10 is a potent activator of pDCs while also acting as a stimulator for B cells. However, the efficacy of G10 is limited when administered in a soluble/unprotected form due to its rapid degradation by DNases. The Qβ protein shell can protect G10 from degradation while also maximizing effective delivery to target TLR-9-expressing cells such as pDCs. After entering pDCs, vidutolimod induces IFN-α secretion, which may potentially promote cytotoxic T cells to kill premalignant cells. We expect that the boosted immune system after in situ vidutolimod injection could actively suppress malignancy progression.
description: To validate this hypothesis, a traditional murine model for inducing oral cancer was used to study leukoplakia development. Vidutolimod was administered with anti-PD1, an immune checkpoint inhibitor to achieve maximal immune response. The effect of treatment was analyzed histologically and immunologically. The immune profile will be revealed through analyzing immune cell populations in oral lesions, draining lymph nodes, and cytokine changes in serum before and after treatment.