PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

Seki, Tomohiro; Saida, Yu; Kishimoto, Shun; Lee, Jisook; Otowa, Yasunori; Yamamoto, Kazutoshi; Chandramouli, Gadisetti V.R.; Devasahayam, Nallathamby; Mitchell, James B.; Krishna, Murali C.; Brender, Jeffrey R.

doi:10.1016/j.neo.2022.100793

Cited by 15 publications

(12 citation statements)

References 53 publications

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“…Perfusion MRI techniques utilising exogenously administered paramagnetic contrast agents may provide more sensitive approaches to inform on tumour vascular changes following HA degradation. Indeed PEGPH20‐mediated improvements in tumour perfusion/permeability and fractional blood volume have been reported in models of PDAC using dynamic contrast enhanced MRI and susceptibility contrast MRI [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Reeves

Zormpas-Petridis

et al. 2023

Molecular Oncology

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Hyaluronan (HA) is a key component of the dense extracellular matrix in breast cancer, and its accumulation is associated with poor prognosis and metastasis. Pegvorhyaluronidase alfa (PEGPH20) enzymatically degrades HA and can enhance drug delivery and treatment response in preclinical tumour models. Clinical development of stromal‐targeted therapies would be accelerated by imaging biomarkers that inform on therapeutic efficacy in vivo. Here, PEGPH20 response was assessed by multiparametric magnetic resonance imaging (MRI) in three orthotopic breast tumour models. Treatment of 4T1/HAS3 tumours, the model with the highest HA accumulation, reduced T1 and T2 relaxation times and the apparent diffusion coefficient (ADC), and increased the magnetisation transfer ratio, consistent with lower tissue water content and collapse of the extracellular space. The transverse relaxation rate R2* increased, consistent with greater erythrocyte accessibility following vascular decompression. Treatment of MDA‐MB‐231 LM2‐4 tumours reduced ADC and dramatically increased tumour viscoelasticity measured by MR elastography. Correlation matrix analyses of data from all models identified ADC as having the strongest correlation with HA accumulation, suggesting that ADC is the most sensitive imaging biomarker of tumour response to PEGPH20.

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Section: Discussionmentioning

confidence: 99%

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Reeves

Zormpas-Petridis

et al. 2023

Molecular Oncology

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“…As a promising therapeutic strategy, PEGylated recombinant human hyaluronidase PH20 (rHuPH20), has been clinically trialed with a focus on prolonging blood circulation times and enhancing drug penetration within tumors. [38,39] However, the enzyme activity might be compromised by the chemical modification of noncleavable PEG chains. Alternatively, researchers have developed a biocompatible polymer-modified HAase via a pH-responsive traceless linker and enabled them to self-assemble into nanoparticles, which is expected to release native HAase in response to the acidic TME.…”

Section: Introductionmentioning

confidence: 99%

Breaking‐Down Tumoral Physical Barrier by Remotely Unwrapping Metal‐Polyphenol‐Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy‐Induced Immune Response

Sun,

Li,

Shen

et al. 2024

Advanced Materials

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The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here we propose a remotely unwrapping strategy of metal‐polyphenol‐packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron‐chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH could be triggered by the intravenously injected DFO, resulting in the release, reactivation and deep penetration of encapsulated HAase inside tumors. Such a cost‐effective HAase delivery strategy memorably improved the subsequent photothermal and photodynamic therapy (PTT/PDT)‐induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross‐talk between tumor and tumor‐draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis and recurrence in multiple mouse cancer models. Overall, this work presents a proof‐of‐concept of the dynamic disassembly of metal‐polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.This article is protected by copyright. All rights reserved

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“…Hypoxia plays a crucial role in the progression and metastasis of many cancers and is strongly correlated with poor prognosis. The success of some therapeutic treatments, such as radiotherapy 1,2 and some types of chemotherapy, 2–6 can also hinge on the oxygen levels within the tumor. These factors have led to the development of various techniques for determining the oxygenation status of tumors 7–10 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range

Kishimoto,

Devasahayam,

Chandramouli

et al. 2023

Magnetic Resonance in Med

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PurposeIn this study, we compared two triarylmethyl (TAM) spin probes, Ox071 and Ox063 for their efficacy in measuring tissue oxygen levels under hypoxic and normoxic conditions by R2*‐based EPR oximetry.MethodsThe R2* dependencies on the spin probe concentration and oxygen level were calibrated using deoxygenated 1, 2, 5, and 10 mM standard solutions and 2 mM solutions saturated at 0%, 2%, 5%, 10%, and 21% of oxygen. For the hypoxic model, in vivo imaging of a MIA PaCa‐2 tumor implanted in the hind leg of a mouse was performed on successive days by R2*‐based EPR oximetry using either Ox071 or Ox063. For the normoxic model, renal imaging of healthy athymic mice was performed using both spin probes. The 3D images were reconstructed by single point imaging and multi‐gradient technique was used to determine R2* maps.ResultsThe signal intensities of Ox071 were approximately three times greater than that of Ox063 in the entire partial pressure of oxygen (pO2) range investigated. The histograms of the tumor pO2 images were skewed for both spin probes, and Ox071 showed more frequency counts at pO2 > 32 mm Hg. In the normoxic kidney model, there was a clear delineation between the high pO2 cortex and the low pO2 medulla regions. The histogram of high‐resolution kidney oximetry image using Ox071 was nearly symmetrical and frequency counts were seen up to 55 mm Hg, which were missed in Ox063 imaging.ConclusionAs an oximetric probe, Ox071 has clear advantages over Ox063 in terms of sensitivity and the pO2 dynamic range.

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PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

Cited by 15 publications

References 53 publications

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Breaking‐Down Tumoral Physical Barrier by Remotely Unwrapping Metal‐Polyphenol‐Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy‐Induced Immune Response

Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range

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PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

Cited by 15 publications

References 53 publications

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography

Breaking‐Down Tumoral Physical Barrier by Remotely Unwrapping Metal‐Polyphenol‐Packaged Hyaluronidase for Optimizing Photothermal/Photodynamic Therapy‐Induced Immune Response

Evaluation of a deuterated triarylmethyl spin probe for in vivo R2∗‐based EPR oximetric imaging with enhanced dynamic range

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Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range