Accession Number : AD1050846


Title :   Novel Approaches to Locoregional and Systemic Immunotherapy for Ovarian Cancer


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : Memorial Sloan Kettering Cancer Center New York United States


Personal Author(s) : Zamarin, Dmitriy


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050846.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 15


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.


Descriptors :   ovarian cancer , immunotherapy , oncolytic viruses , t lymphocytes , inhibitors , biological markers , neoplasms , immune system , immunomodulation


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE