%0 Journal Article
%T Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression
%A Amy B. Heimberger
%A Brett Schrand
%A Eli Gilboa
%A Ganesh Rao
%A George Calin
%A Gregory N. Fuller
%A Jun Wei
%A Konrad Gabrusiewicz
%A Ling-Yuan Kong
%A Shouhao Zhou
%J Archive of "Oncoimmunology".
%D 2016
%R 10.1080/2162402X.2015.1117739
%X High-grade gliomas are notoriously heterogeneous regarding antigen expression, effector responses, and immunosuppressive mechanisms. Therefore, combinational immune therapeutic approaches are more likely to impact a greater number of patients and result in longer, durable responses. We have previously demonstrated the monotherapeutic effects of miR-124, which inhibits the signal transducer and activator of transcription 3 (STAT3) immune suppressive pathway, and immune stimulatory 4¨C1BB aptamers against a variety of malignancies, including genetically engineered immune competent high-grade gliomas. To evaluate potential synergy, we tested an immune stimulatory aptamer together with microRNA-124 (miRNA-124), which blocks tumor-mediated immune suppression, and found survival to be markedly enhanced, including beyond that produced by monotherapy. The synergistic activity appeared to be not only secondary to enhanced CD3+ cell numbers but also to reduced macrophage immune tumor trafficking, indicating that a greater therapeutic benefit can be achieved with approaches that both induce immune activation and inhibit tumor-mediated immune suppression within the central nervous system (CNS) tumors
%K Aptamer
%K CNS
%K gliomas
%K microRNA
%K STAT3
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910740/