TY - JOUR
T1 - HER2-targeted polyinosine/polycytosine therapy inhibits tumor growth and modulates the tumor immune microenvironment
AU - Zigler, Maya
AU - Shir, Alexei
AU - Joubran, Salim
AU - Sagalov, Anna
AU - Klein, Shoshana
AU - Edinger, Nufar
AU - Lau, Jeffrey
AU - Yu, Shang Fan
AU - Mizraji, Gabriel
AU - Levin, Anat Globerson
AU - Sliwkowski, Mark X.
AU - Levitzki, Alexander
N1 - Publisher Copyright:
©2016 American Association for Cancer Research.
PY - 2016
Y1 - 2016
N2 - The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits; however, patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study, we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vectorinduced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immunocompetent mice. The data presented here could open additional avenues in the treatment of HER2-positive breast cancer.
AB - The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits; however, patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study, we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vectorinduced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immunocompetent mice. The data presented here could open additional avenues in the treatment of HER2-positive breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=84985995356&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-15-0203
DO - 10.1158/2326-6066.CIR-15-0203
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C2 - 27241844
AN - SCOPUS:84985995356
SN - 2326-6066
VL - 4
SP - 688
EP - 697
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 8
ER -
