Immunomodulatory effects of intravenous BIS-1 F(ab')2 administration in renal cell cancer patients.
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.
Janssen
R A
RA
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Kroesen
B J
BJ
Buter
J
J
Mesander
G
G
Sleijfer
D T
DT
The
T H
TH
Mulder
N H
NH
de Leij
L
L
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018033:Antibodies, Bispecific / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism / Q000627:therapeutic use; D016233:Immunotherapy, Active; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D007970:Leukopenia / Q000139:chemically induced; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007128:Immunoglobulin Fragments; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha