Dr. Samir Khleif, Director of the State of Georgia Cancer Center, Georgia Regents University Cancer Center and The Cancer Service Line
Tumor-Immune System Interaction
- Samir N. Khleif, MD, director of the State of Georgia Cancer Center, Georgia Regents University Cancer Center, and the Cancer Service Line; Board of Directors, Advaxis, Inc.; formerly chief of the Cancer Vaccine Section at the National Cancer Institute and Special Assistant to the Commissioner of the U.S. Food and Drug Administration (FDA) for oncology, presented the rationale for and preclinical data supporting planned and ongoing combination studies of Lm-LLO immunotherapy with other immune-targeted anticancer agents.
- Dr Khleif described the role of the TME in mediating the success or failure of immunotherapeutics. Generation of cytotoxic immune effector T cells against the tumor is the first step, but the TME actively seeks to inactivate the effectors through the presence of immune suppressive cytokines, and recruitment of Tregs, MDSCs, and other inhibitors of the local immune response.
- Lm-LLO immunotherapies both act as a peptide vaccine to activate tumor-specific effector T cells and work to generate a “friendly” TME with a positive effector-to-Tregs cell ratio.
- Opportunity to further enhance the activity of Lm-LLO by positively regulating the TME to further reduce effector cell inactivation, increase the number or activity of effector cells, or simultaneously stimulate other aspects of the immune response may be achieved through combination therapy approaches
- Dr Khleif presented preclinical data demonstrating the synergistic activity of Lm-LLO and anti-programmed cell death protein 1 (PD1) monoclonal antibody therapy in tumor models, which has formed the basis for ongoing or planned clinical study of this combination approach.