PMID: 11309350Apr 20, 2001Paper

Efficacy of local versus systemic application of antibody-cytokine fusion proteins in tumor therapy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
O ChristM Zöller

Abstract

Application of immunocytokines [fusion proteins (FuPs)] where the cytokine has been coupled to an antibody may not produce the severe side effects frequently observed during systemic application of cytokines in cancer therapy. However, it has not been explored whether FuPs are sufficient for intratumoral activation of leukocytes or whether intratumoral versus systemic application may be of greater efficacy. Interleukin 2 (IL2) or tumor necrosis factor (TNF) coupled to an anti-epidermal growth factor receptor monoclonal antibody (IL2-FuP or TNF-FuP) were tested in SCID mice bearing a human epidermal growth factor receptor-positive melanoma transplant and being reconstituted with human HLA-matched peripheral blood leukocytes. Whole-body autoradiography revealed larger accumulation and prolonged retention of i.v. or intratumorally applied IL2-FuP or TNF-FuP compared with the antibody. Even with low doses of FuP, tumor growth was significantly retarded, with the survival time being further prolonged by the intratumoral application. Furthermore, outgrowth of the tumor was prevented in approximately 50% of mice as long as they received weekly injections of peripheral blood leukocytes concomitantly with the FuPs, which confirmed that ...Continue Reading

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.