TY - JOUR
T1 - Intracranial injection of genetically modified, mosquito non-transmissible Zika virus
T2 - Safety in primates and ramifications for brain tumor therapy
AU - Hirsch, Alec J.
AU - de Andrade Costa, Amanda
AU - German, Cody
AU - Parkins, Christopher J.
AU - Smith, Jessica L.
AU - Russler-Germain, Emilie
AU - Kesarwani, Ashwani
AU - Li, Yuping
AU - Carlson, Verginia Cuzon
AU - Carlson, Timothy
AU - McBride, Jodi L.
AU - Srinivasan, Sathya
AU - Lewis, Anne D.
AU - Xie, Xuping
AU - Shi, Pei Yong
AU - Diamond, Michael S.
AU - Chheda, Milan G.
N1 - Publisher Copyright:
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2025/12/16
Y1 - 2025/12/16
N2 - Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.
AB - Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.
KW - Zika virus
KW - glioblastoma
KW - oncolytic virus
KW - rhesus macaque
UR - https://www.scopus.com/pages/publications/105025172004
U2 - 10.1016/j.xcrm.2025.102509
DO - 10.1016/j.xcrm.2025.102509
M3 - Article
C2 - 41406941
AN - SCOPUS:105025172004
SN - 2666-3791
VL - 6
SP - 102509
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 12
ER -