Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms

• DOI: 10.1038/s41467-017-00324-x
• Publication Date: 2017-08-17T19:45:01Z
• Authors: Dae-Sun Kim; Himika Dastidar; Chunfen Zhang; Franz J. Zemp; Keith Lau; Matthias Ernst; Andrea Rakic; Saif Sikdar; Jahanara Rajwani; Victor Naumenko; Dale R. Balce; Ben W. Ewanchuk; Pankaj Tailor; Robin M. Yates; Craig Jenne; Chris Gafuik; Douglas J. Mahoney
• Keywords: 0301 basic medicine; 570; Science; 610; Antineoplastic Agents; CD8-Positive T-Lymphocytes; Article; Vesicular stomatitis Indiana virus; Mitochondrial Proteins; Mice; 03 medical and health sciences; Biomimetic Materials; Cell Line, Tumor; Animals; Humans; Oncolytic Virotherapy; Mice, Inbred BALB C; Q; Intracellular Signaling Peptides and Proteins; Neoplasms, Experimental; Combined Modality Therapy; 3. Good health; Mice, Inbred C57BL; Oncolytic Viruses; Thiazoles; Treatment Outcome; Female; Apoptosis Regulatory Proteins

Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound virus therapies also modulate host immune responses in ways we hypothesized would complement one another promoting anticancer T-cell immunity. We show that synergize driving CD8