Abstract | PURPOSE: METHODS: The efficacy of ADCs, antibodies, TMZ and radiation was tested in xenograft models of GBM, U-87MG and U-87MG EGFRvIII. Both models express EGFR. U-87MG EGFRvIII was transduced to express EGFRvIII. Changes in tumor volume, biomarkers of cell death and apoptosis after treatment were used to measure efficacy of the various treatments. Synergism of depatux-m and TMZ was verified in three-dimensional cultures of U-87MG and U-87MG EGFRvIII by the method of Chou and Talalay. RESULTS: Combined with TMZ and radiotherapy (RT), depatux-m inhibited xenograft growth of U-87MG and U-87MG EGFRvIII more than either treatment with depatux-m or TMZ + RT. Durability of the response to depatux-m + TMZ + RT or depatux-m + TMZ was more pronounced in U-87MG EGFRvIII than in U-87MG. Efficacy of depatux-m + TMZ was synergistic in U-87MG EGFRvIII and additive in U-87MG. CONCLUSION: Adding depatux-m enhances the efficacy of standard of care therapy in preclinical models of GBM. Durability of response to depatux-m + TMZ in vivo and synergy of the drug-drug interaction correlates with the amount of antigen expressed by the tumor cells.
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Authors | Kedar S Vaidya, Michael J Mitten, Adelyn L Zelaya-Lazo, Anatol Oleksijew, Cory Alvey, Hugh D Falls, Sasmita Mishra, Joann Palma, Peter Ansell, Andrew C Phillips, Edward B Reilly, Mark Anderson, Erwin R Boghaert |
Journal | Journal of neuro-oncology
(J Neurooncol)
Vol. 152
Issue 2
Pg. 233-243
(Apr 2021)
ISSN: 1573-7373 [Electronic] United States |
PMID | 33517558
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- EGFR protein, human
- ErbB Receptors
- depatuxizumab mafodotin
- Temozolomide
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Brain Neoplasms
(genetics, pathology)
- Cell Proliferation
(drug effects)
- Disease Models, Animal
- Drug Synergism
- ErbB Receptors
(genetics)
- Glioblastoma
(genetics, pathology)
- Humans
- Mice
- Temozolomide
(pharmacology)
- Xenograft Model Antitumor Assays
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