Multiple treatment cycles of neural stem cell delivered oncolytic adenovirus for the treatment of glioblastoma

Jennifer Batalla-Covello; Hoi Wa Ngai; Linda Flores; Marisa McDonald; Caitlyn Hyde; Joanna Gonzaga; Mohamed Hammad; Margarita Gutova; Jana Portnow; Tim Synold; David T. Curiel; Maciej S. Lesniak; Karen S. Aboody; Rachael Mooney

doi:10.3390/cancers13246320

Multiple treatment cycles of neural stem cell delivered oncolytic adenovirus for the treatment of glioblastoma

Jennifer Batalla-Covello, Hoi Wa Ngai, Linda Flores, Marisa McDonald, Caitlyn Hyde, Joanna Gonzaga, Mohamed Hammad, Margarita Gutova, Jana Portnow, Tim Synold, David T. Curiel, Maciej S. Lesniak, Karen S. Aboody^*, Rachael Mooney

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Tumor tropic neural stem cells (NSCs) can improve the anti-tumor efficacy of oncovirotherapy agents by protecting them from rapid clearance by the immune system and delivering them to multiple distant tumor sites. We recently completed a first-in-human trial assessing the safety of a single intracerebral dose of NSC-delivered CRAd-Survivin-pk7 (NSC.CRAd-S-pk7) combined with radiation and chemotherapy in newly diagnosed high-grade glioma patients. The maximum feasible dose was determined to be 150 million NSC.CRAd-Sp-k7 (1.875 × 10¹¹ viral particles). Higher doses were not assessed due to volume limitations for intracerebral administration and the inability to further concentrate the study agent. It is possible that therapeutic efficacy could be maximized by administering even higher doses. Here, we report IND-enabling studies in which an improvement in treatment efficacy is achieved in immunocompetent mice by administering multiple treatment cycles intracerebrally. The results imply that pre-existing immunity does not preclude therapeutic benefits attainable by administering multiple rounds of an oncolytic adenovirus directly into the brain.

Original language	English (US)
Article number	6320
Journal	Cancers
Volume	13
Issue number	24
DOIs	https://doi.org/10.3390/cancers13246320
State	Published - Dec 1 2021

Keywords

Glioma
Immunotherapy
Neural stem cell
Oncolytic virus
Stem cell carrier
Viral delivery

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers13246320

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Batalla-Covello, J., Ngai, H. W., Flores, L., McDonald, M., Hyde, C., Gonzaga, J., Hammad, M., Gutova, M., Portnow, J., Synold, T., Curiel, D. T., Lesniak, M. S., Aboody, K. S., & Mooney, R. (2021). Multiple treatment cycles of neural stem cell delivered oncolytic adenovirus for the treatment of glioblastoma. Cancers, 13(24), [6320]. https://doi.org/10.3390/cancers13246320

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abstract = "Tumor tropic neural stem cells (NSCs) can improve the anti-tumor efficacy of oncovirotherapy agents by protecting them from rapid clearance by the immune system and delivering them to multiple distant tumor sites. We recently completed a first-in-human trial assessing the safety of a single intracerebral dose of NSC-delivered CRAd-Survivin-pk7 (NSC.CRAd-S-pk7) combined with radiation and chemotherapy in newly diagnosed high-grade glioma patients. The maximum feasible dose was determined to be 150 million NSC.CRAd-Sp-k7 (1.875 × 1011 viral particles). Higher doses were not assessed due to volume limitations for intracerebral administration and the inability to further concentrate the study agent. It is possible that therapeutic efficacy could be maximized by administering even higher doses. Here, we report IND-enabling studies in which an improvement in treatment efficacy is achieved in immunocompetent mice by administering multiple treatment cycles intracerebrally. The results imply that pre-existing immunity does not preclude therapeutic benefits attainable by administering multiple rounds of an oncolytic adenovirus directly into the brain.",

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author = "Jennifer Batalla-Covello and Ngai, {Hoi Wa} and Linda Flores and Marisa McDonald and Caitlyn Hyde and Joanna Gonzaga and Mohamed Hammad and Margarita Gutova and Jana Portnow and Tim Synold and Curiel, {David T.} and Lesniak, {Maciej S.} and Aboody, {Karen S.} and Rachael Mooney",

note = "Funding Information: Funding: This research was funded by the City of Hope, the Anthony F. & Susan M. Markel Foundation, the Ben and Catherine Ivy Foundation, the Bob Marx Board of Governors Foundation, the Rally Foundation, the Rosaline and Arthur Gilbert Foundation, the California Institute of Regenerative Medicine (TRAN1-11544), the Alvarez Family Charitable Foundation, the H.W.N. & Frances Berger Foundation Fellowship, the Norman & Melinda Payson Fellowship, Cancer Center Support Grant (P30 CA33572), and City of Hope{\textquoteright}s Irell & Manella Graduate School of Biological Sciences. Research reported in this publication included work performed by Holly Yin from the City of Hope Molecular Pathology Core, which is supported by the National Cancer Institute of the NIH under award number P30CA033572. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).",

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AU - Hyde, Caitlyn

AU - Gonzaga, Joanna

AU - Hammad, Mohamed

AU - Gutova, Margarita

AU - Portnow, Jana

AU - Synold, Tim

AU - Curiel, David T.

AU - Lesniak, Maciej S.

AU - Aboody, Karen S.

AU - Mooney, Rachael

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N2 - Tumor tropic neural stem cells (NSCs) can improve the anti-tumor efficacy of oncovirotherapy agents by protecting them from rapid clearance by the immune system and delivering them to multiple distant tumor sites. We recently completed a first-in-human trial assessing the safety of a single intracerebral dose of NSC-delivered CRAd-Survivin-pk7 (NSC.CRAd-S-pk7) combined with radiation and chemotherapy in newly diagnosed high-grade glioma patients. The maximum feasible dose was determined to be 150 million NSC.CRAd-Sp-k7 (1.875 × 1011 viral particles). Higher doses were not assessed due to volume limitations for intracerebral administration and the inability to further concentrate the study agent. It is possible that therapeutic efficacy could be maximized by administering even higher doses. Here, we report IND-enabling studies in which an improvement in treatment efficacy is achieved in immunocompetent mice by administering multiple treatment cycles intracerebrally. The results imply that pre-existing immunity does not preclude therapeutic benefits attainable by administering multiple rounds of an oncolytic adenovirus directly into the brain.

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Multiple treatment cycles of neural stem cell delivered oncolytic adenovirus for the treatment of glioblastoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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