Poster abstracts
Poster number 66 submitted by Uttam Goruganthu
Monovalent form of Jagged1 (sJag1) is an immunomodulatory agent
Uttam Goruganthu (MCDB), Longzhu Piao (Internal Medicine), Mikhail Dikov (Internal Medicine), Dr David P Carbone (Internal Medicine)
Abstract:
Objective: Notch receptor-ligand interactions are an important regulatory point governing specific types of T cell-mediated immune responses through variable expression of Notch ligands in antigen presenting cells. We hypothesized that monovalent Notch-Jagged1 interactions will inhibit signaling and overcome tumor-mediated immune suppression. Preliminary data indicates that the administration of soluble, monovalent Jagged1, a Notch ligand, to tumor bearing mice significantly reduced tumor burden, enhanced anti-tumor immunity and improved overall survival compared to untreated tumor-bearing mice.
Methods: We used a syngeneic lung cancer murine model (LLC+C57BL6) to evaluate the immune efficacy of sJag1. Immunostaining followed by FACS was used to analyze immune cell populations, ELISPOT was used to quantitate cytokine production.
Results: Preliminary data shows that treating tumor-bearing mice with monomeric murine Jag1 (comprised of the first three N-terminal domains) elicited antigen-specific T-cells. Blockade of Jag1-mediated Notch signaling significantly reduced Tregs in spleen and lymph nodes, improved anti-tumor immunity, attenuated tumor growth, increased IFN-γ production by splenocytes and improved survival compared to untreated controls.
Conclusions: Data suggest a role of sJag1 in improving anti-tumor T cell responses and provides a strong rationale for the clinical application of functional soluble fragments of Jag1 to improve anti-tumor immune responses.
Keywords: antitumor immunity, notch signaling, lung cancer