Novel Approaches to Locoregional and Systemic Immunotherapy for Ovarian Cancer
Abstract
The goals of our research are to understand the mechanisms of recognition of ovarian cancer by the immune system, to develop peripheral and tissue-based biomarkers predictive of response to anti-PD-1-based therapeutic approaches, and to identify/develop new combinatorial therapeutic strategies based on systemic and locoregional immune targeting approaches. Our research over the past year has generated several findings. First, we characterized peripheral blood populations in patients with ovarian cancer treated with immune checkpoint blockade and found that these treatments are associated with upregulation of additional immune checkpoints such as LAG-3, providing rationale for further combinations. Secondly, we have found that tumors exhibiting low mutational burden can still exhibit high levels of T cell infiltration, which is generating new research directions, prompting us to examine the interaction between the tumor-intrinsic driver pathways and the immune system. Third, we have initiated animal studies using intratumoral modulation with recombinant oncolytic Newcastle Disease Virus (NDV). While looking for the most effective combination of recombinant NDV with systemic immunomodulatory agents, we found that pre-existing immunity to the virus potentiates, rather than inhibits its therapeutic efficacy. This finding indicates that patients undergoing such treatments may benefit from therapy even if they develop neutralizing anti-viral antibodies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1050846
Entities
People
- Dmitriy Zamarin
Organizations
- Memorial Sloan Kettering Cancer Center