Enhanced effects of monoclonal antibody carboplatin immunoconjugates uptake and anti-tumor effects with angiotensin II and tumor necrosis factor.
The most important factor influencing the use of monoclonal antibody immunoconjugates for cancer treatment is effectiveness of enhancement for tumor targeting. We call attention to the vasoactive agents angiotensin II (ATII) for selective increase in tumor blood flow and cytokine tumor necrosis factor (TNF) to improve the vascular permeability of the tumor. Tumor localization and biodistribution were investigated by nude mice transplanted human colon adenocarcinoma (LS-180) with radiolabeled carboplatin immunoconjugates. Tumor activity 48 h after administration of ATII and TNF was significantly higher than in the control group. However, nonspecific accumulation in normal organs was not observed. In vivo anti-tumor effects in animals with ATII and TNF was significantly stronger than in those given the same dose drug alone or immunoconjugates alone. These results indicate that ATII and TNF could be useful tools for induction of stronger inhibition of tumor growth without systemic toxicity.
D000230:Adenocarcinoma / Q000098:blood supply* / Q000737:chemistry / Q000188:drug therapy; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000187:drug effects; D016190:Carboplatin / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000188:drug therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*