RARE-10. ADAMANTINOMATOUS CRANIOPHARYNGIOMA RESIDES OUTSIDE THE BLOOD BRAIN BARRIER
| Autor: | Trinka Vijmasi, Lindsey Hoffman, Eric Prince, Kimberly R. Jordan, Jennifer A. McWilliams, Susan Staulcup, Kathleen Dorris, Nicholas K. Foreman, Astrid C Hengartner, Todd C. Hankinson |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Fetus Pathology medicine.medical_specialty Base of skull business.industry Ficoll Blood–brain barrier medicine.disease Preoperative care Rathke's pouch Epithelium Craniopharyngioma medicine.anatomical_structure Oncology medicine AcademicSubjects/MED00300 AcademicSubjects/MED00310 Neurology (clinical) business Craniopharyngioma and Rare Tumors |
| Zdroj: | Neuro-Oncology |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | BACKGROUND Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. Genetically engineered mouse models of ACP demonstrate that perturbation of the fetal anterior pituitary can generate tumors analogous to ACP. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control, with the most common agent being the humanized monoclonal antibody, tocilizumab. This agent demonstrated poor blood-brain barrier (BBB) penetration in primates. We present findings from two children enrolled on a phase 0 clinical trial (NCT03970226) of a single dose of preoperative intravenous tocilizumab prior to resection of newly diagnosed ACP. METHODS Blood samples were obtained at multiple timepoints. Serum was isolated via ficoll separation. Tumor tissue and cyst fluid were obtained 4–6 hours following the single IV dose of tocilizumab. Tissue was snap-frozen. Tumor was homogenized in RIPA buffer. Free tocilizumab in serum, cyst fluid, and tumor tissue was measured using enzyme-linked immunosorbent assay (ELISA) against a standard curve. RESULTS Both patients in this trial demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and tumor tissue, compared to undetectable levels in control samples. CONCLUSION ACP resides outside BBB protection. In addition to demonstrating the feasibility of systemic delivery of tocilizumab, these findings indicate that other large molecules, including those known to have poor BBB penetration, may be systemically delivered as part of an antitumor regimen in the treatment of ACP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|