Novel radioimmunotherapy for lymphoma and solid tumours both as a single agent and in combination with the vascular disrupting agents

摘要: Background: Single-agent radioimmunotherapy (RIT) has demonstrated efficacy in B-cell lymphomas but been relatively disappointing solid tumours. To improve its combinations of RIT with new agents are being investigated. One rational combination, from preclinical studies, is and a vascular disrupting agent (VDA). Aim: complete two Phase I clinical studies: 1) using single-agent Hodgkin lymphoma (HL) T-cell Lymphomas 2) combining with Combretastatin-A4-Phosphate (CA4P) for Angiogenic cytokines and circulating cells were investigated as potential biomarkers VDA induced hypoxia. Methods: Two phase I, open-label, non-randomised dose-escalation trials were completed. In the lymphomas murine CD25-antibody conjugated to 131I was used 14 patients. CEA-expressing gastrointestinal tumours an anti-CEA (carcino-embryonic antigen) antibody, A5B7 was used CA4P 12 patients. ELISA (enzyme-linked immunosorbent assay) measured angiogenic cytokines in serum flow cytometry assessed Tie-2 monocytes EPC’s. Hepatic artery embolisation model acute tumour hypoxia. Results: The 131I-CHT25 study response rate 67% at or above MTD (maximum tolerated dose). 131I-A5B7 CA4P produced one minor corresponding marker fall. Erythropoietin, VEGF (vascular endothelial growth factor) monocytes increased post embolisation would merit further investigation biomarkers. Angiopoietin 2 appeared elevated both malignancy liver disease independent prognostic factor did not rise postembolisation. This supported previous work suggesting angiopoietin-2 was derived surrounding liver rather than tumour. Conclusion: Single agent appears effective lymphoma research required in More potent VDAs have since entered the development determine will be vital. VEGF, erythropoietin, EPC’s for that role.