Immunomodulatory effects of intravenous BIS-1 F(ab')2 administration in renal cell cancer patients.

Abstract

We report the immunomodulatory effects of an intravenous treatment with F(ab')2 fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the EGP-2 molecule on carcinoma cells and some normal epithelia. The amount of BIS-1 F(ab')2 bound to peripheral blood lymphocytes (PBLs) increased dose-dependently. This occupation degree was highest at the end of the 2 h infusion and rapidly decreased subsequently. During the first hour of BIS-1 F(ab')2 infusion the number of PBLs decreased slowly. This was followed by an increase in serum tumour necrosis factor alpha (TNF-alpha) concentrations and a rapid decrease in the numbers of peripheral blood lymphocytes, monocytes and eosinophils. In our view, the most likely explanation for the observed decrease in occupation degree of BIS-1 F(ab')2 and the rise in TNF-alpha levels is based on the assumption that BIS-1-carrying T cells leave the circulation. The CD3 antigens on these extravasated T cells become cross-linked by EGP-2 antigens, inducing TNF-alpha secretion. This results in an enhanced decrease in the numbers of PBLs, monocytes and eosinophils. These preliminary results suggest that BIS-1 F(ab')2 treatment during IL-2 therapy may induce local T-cell activation.

• Authors: R A Janssen, B J Kroesen, J Buter, G Mesander, D T Sleijfer, T H The, N H Mulder, L de Leij
• Journal: British journal of cancer (Br J Cancer) Vol. 72 Issue 3 Pg. 795-9 (Sep 1995) ISSN: 0007-0920 [Print] England
• PMID: 7669598 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Bispecific
• Antigens, Neoplasm
• Cell Adhesion Molecules
• Epithelial Cell Adhesion Molecule
• Immunoglobulin Fragments
• Interleukin-2
• Tumor Necrosis Factor-alpha

Topics

• Adjuvants, Immunologic (metabolism, pharmacokinetics, therapeutic use)
• Antibodies, Bispecific (metabolism, pharmacokinetics, therapeutic use)
• Antigens, Neoplasm (pharmacology)
• Carcinoma, Renal Cell (immunology, metabolism, therapy)
• Cell Adhesion Molecules (pharmacology)
• Epithelial Cell Adhesion Molecule
• Humans
• Immunoglobulin Fragments (metabolism, therapeutic use)
• Immunotherapy, Active
• Injections, Intravenous
• Interleukin-2 (therapeutic use)
• Kidney Neoplasms (immunology, metabolism, therapy)
• Leukopenia (chemically induced)
• Lymphocyte Activation (drug effects)
• T-Lymphocytes (immunology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)