Glioblastoma model mouse rescue from mortality by brain-targeted catalytically-enhanced angiotensin-converting enzyme 2 mutant-antibody fusion protein
- 1Duke University
Abstract
We have discovered that an engineered angiotensin-converting enzyme 2 (ACE2)-brain-targeted antibody fusion protein, referred to as ACE2dm-s1, improves survival of CT-2A xenograft glioblastoma (GBM) model mice when administered in combination with a small molecule STING agonist cancer therapeutic. Particularly striking about these survival results is that prior efforts that used losartan, a small molecule angiotensin receptor antagonist that acts on the same Renin-Angiotensin System (RAS) axis that is affected by the action of ACE2dm-s1, showed that this small molecule provided no survival benefit when used as an element of combination therapy in the same CT-2A GBM model used in our experiments. The improved CT-2A mouse survival, which was not observed for ACE2dm-s1 or STING agonist monotherapy, combines with our flow cytometry study results that revealed an ACE2dm-s1-mediated shift of brain immune cell populations toward an anti-tumoral composition to establish ACE2dm-s1's utility as a tumor microenvironment (TME) modulator that could serve as an adjuvant in increasing the efficacy of wide range of cancer treatment modalities including chemotherapeutic agents, immune checkpoint inhibitors, and CAR-T cells.
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BibTeX
@misc{heinzelman2026glioblastoma,
title = {{Glioblastoma model mouse rescue from mortality by brain-targeted catalytically-enhanced angiotensin-converting enzyme 2 mutant-antibody fusion protein}},
author = {P. Heinzelman and G. R. Nageeb and J. Choi and J. Liu and S. Y. Lee and P. A. Romero and M. Lim},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.763994},
url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763994v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Glioblastoma model mouse rescue from mortality by brain-targeted catalytically-enhanced angiotensin-converting enzyme 2 mutant-antibody fusion protein
AU - P. Heinzelman
AU - G. R. Nageeb
AU - J. Choi
AU - J. Liu
AU - S. Y. Lee
AU - P. A. Romero
AU - M. Lim
PY - 2026
DA - 2026/11/03
PB - bioRxiv
DO - 10.64898/2026.11.03.763994
UR - https://www.biorxiv.org/content/10.64898/2026.11.03.763994v1
AB - We have discovered that an engineered angiotensin-converting enzyme 2 (ACE2)-brain-targeted antibody fusion protein, referred to as ACE2dm-s1, improves survival of CT-2A xenograft glioblastoma (GBM) model mice when administered in combination with a small molecule STING agonist cancer therapeutic. Particularly striking about these survival results is that prior efforts that used losartan, a small molecule angiotensin receptor antagonist that acts on the same Renin-Angiotensin System (RAS) axis that is affected by the action of ACE2dm-s1, showed that this small molecule provided no survival benefit when used as an element of combination therapy in the same CT-2A GBM model used in our experiments. The improved CT-2A mouse survival, which was not observed for ACE2dm-s1 or STING agonist monotherapy, combines with our flow cytometry study results that revealed an ACE2dm-s1-mediated shift of brain immune cell populations toward an anti-tumoral composition to establish ACE2dm-s1's utility as a tumor microenvironment (TME) modulator that could serve as an adjuvant in increasing the efficacy of wide range of cancer treatment modalities including chemotherapeutic agents, immune checkpoint inhibitors, and CAR-T cells.
ER -