Targeting Ubiquitin-like Protein, ISG15, as a Novel Tumor Associated Antigen in Colorectal Cancer

• Published in: Cancers Vol. 15; no. 4; p. 1237
• Main Authors: Nguyen, Hong-My, Gaikwad, Shreyas, Oladejo, Mariam, Paulishak, Wyatt, Wood, Laurence M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Animal models; Antibodies; Antigen (tumor-associated); Antigens; Cancer; Cancer vaccines; Cells; Colorectal cancer; Colorectal carcinoma; Cytotoxicity; Drug targeting; Drug therapy; Effector cells; Experiments; Health aspects; Health sciences; Immune checkpoint inhibitors; Immunoregulation; Immunotherapy; Interferon; interferon-stimulated gene 15; Laboratory animals; Listeria; Listeria-based vaccines; Lymphocytes T; Methods; Proteins; Therapeutic applications; Therapeutic targets; Tumor microenvironment; Tumors; Ubiquitin; Vaccines; United States; United States > US; Texas; colorectal cancer; interferon-stimulated gene 15; Listeria-based vaccines
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15041237

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in both men and women in the United States. While immune checkpoint inhibitor (ICI) therapy is demonstrating remarkable clinical responses, the resistance and immune-related toxicities associated with ICIs demonstrate the need to develop additional immunotherapy options for CRC patients. Cancer vaccines represent a safe and promising treatment approach for CRC. As previously developed tumor-associated antigen (TAA)-based cancer vaccines for CRC are not demonstrating promising results, we propose that interferon-stimulated gene 15 (ISG15) is a novel TAA and therapeutic target for CRC. Our work demonstrates the anti-tumor efficacy of a Listeria-based vaccine targeting ISG15, designated Lm-LLO-ISG15, in an immunocompetent CRC murine model. The Lm-LLO-ISG15-mediated anti-tumor response is associated with an increased influx of functional T cells, higher production of multiple intracellular cytokines response, a lower number of regulatory T cells, and a greater ratio of effector to regulatory T cells (T /T ) in the tumor microenvironment.