Hyaluronan assessment in tumor microenvironment using new affinity histochemistry assay and scoring method
| Autor: | Xionghua W. Wu, Carrie Aldrich, Junming Zhu, Paco Delgado, Sihem Khelifa, Michelle Quiroz, Jie Pu, Ping Jiang, Thomas Müller |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 35:e23196-e23196 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | e23196 Background: Enzymatic degradation of hyaluronan (HA) by PEGylated recombinant human hyaluronidase PH20 (PEGPH20) induces a remodeling of the tumor microenvironment that impacts tumor behavior and response to therapy. Ventana Medical Systems, Inc., (VMSI) and Halozyme Therapeutics co-developed the VENTANA HA RxDx Assay and a scoring method to evaluate HA in solid tumors to potentially predict which patients might better respond to the addition of PEGPH20 to cancer treatments. Methods: Using Halozyme’s novel recombinant HA binding probe altered to include a rabbit Fc region, VMSI developed a highly specific and sensitive affinity histochemistry assay that binds to HA in tissues. Histological features and staining patterns of 106 samples from Halozyme’s 109-202 Phase 2 study of PEGPH20 combined with nab-paclitaxel plus gemcitabine (AG) vs. AG alone in patients with previously untreated stage IV pancreatic ductal adenocarcinoma (PDA) with clinical outcome data were analyzed to develop a scoring method evaluating HA accumulation. Results: A novel scoring algorithm focused solely on the extracellular matrix (ECM) was developed. An ECM HA staining ≥ 50% of the entire tumor surface at any intensity defines an HA-High PDA. We recommend that a 0.05 cm x 0.2 cm uninterrupted fragment of tumor cells and associated stroma obtained using needle gauges of 16 to 20 G as the minimally required amount of tissue to assess HA in PDA. Based on verification studies performed by VMSI, including an inter-reader precision study with a 94% agreement rate, VMSI scoring method proved to be trainable, reproducible, and transferable to pathologists, supporting an IDE approval for selecting patients in the Phase 3 HALO 109-301 study. Conclusions: Performance of the VENTANA HA RxDx Assay, a robust affinity histochemical assay, has been successfully verified in PDA. Two Halozyme clinical studies in PDA (Phase 2 HALO 109-202 Stage 2 & ongoing Phase 3 HALO 109-301) are expected to validate the VMSI HA scoring method in selecting patients who might better respond to the addition of PEGPH20 to cancer treatments. Current Phase 1/2 studies are exploring the utility of the VENTANA HA RxDx Assay and the pantumor potential of PEGPH20. |
| Databáze: | OpenAIRE |
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