Evaluation of submicron particle docetaxel directly injected into uro-oncologic xenografts

Autor:	Sara Dafoe, Ashley Tornio, Michael Frost, Gere S. diZerega, Leanne Drummond, Holly Maulhardt, Lauren M Peterson
Rok vydání:	2019
Předmět:	Cancer Research business.industry 03 medical and health sciences 0302 clinical medicine Transitional cell bladder carcinoma Oncology Docetaxel 030220 oncology & carcinogenesis Clear Cell Renal Carcinoma Cancer research medicine Particle business 030215 immunology medicine.drug
Zdroj:	Journal of Clinical Oncology. 37:360-360
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2019.37.7_suppl.360
Popis:	360 Background: We evaluated intratumoral (IT) injection of submicron particles of pure docetaxel (NanoDoce) into clear cell renal carcinoma (768-O [R]), transitional cell bladder carcinoma (UM-UC-3 [B]) and prostate carcinoma (PC-3 [P]) xenografts implanted into immunocompromised rats and mice. Methods: Animals received IT NanoDoce and IV docetaxel per Table. Treatments were 7 days apart. Animals were followed up to 60 days post-treatment initiation. Tumor size, clinical signs and body weight were assessed 2-3 times per week. In the 786-O and UM-UC-3 studies, tumor site tissues were analyzed for docetaxel levels and H&E and IHC (CD11b, CD45r) was evaluated. Results: Tumor volume decreases with 2 and 3 doses of NanoDoce were significantly greater than (R, B) or similar (P) to IV docetaxel and better than vehicle (p < 0.05). High tissue levels of docetaxel were detected in all NanoDoce-treated animals with evaluable tumor tissue. In these animals, histology confirmed tumor volume findings; IHC showed (peri)tumor-infiltrating immune cells in all NanoDoce-treated animals. Comparators exhibited limited to no infiltration. NanoDoce-treated UM-UC-3 tumor injection sites were typically cleared of tumor and contained lymphoid structures. No lymphoid structures were seen in comparators and all had residual tumor. Conclusions: Local presence of persistent, therapeutic levels of docetaxel from IT NanoDoce creates a unique disruption of the tumor microenvironment. IT injection of NanoDoce may kill tumor cells through direct and indirect means. NanoDoce directly inhibits tumor cell mitosis, and in reducing tumor burden, indirectly promotes immune cell-mediated tumor clearance. Clinical testing of NanoDoce in urogenital tumors is underway. [Table: see text]
Databáze:	OpenAIRE
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