Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.
Antibody targeted therapy of cancer results in anti-antibody production which prevents repeated treatment. Cyclosporin A (CsA) has been used to suppress this response in patients treated with a radiolabelled antibody to carcinoembryonic antigen (CEA). Patients with CEA producing tumours received a minimum of two courses consisting of an injection of radiolabelled antibody and CsA, 24 mg kg-1 day-1, for 6 days; each course was given at 2 week intervals. Two weeks after the completion of the second course the mean human antimouse antibody (HAMA) levels were 3.5 micrograms ml-1 (s.d. 2.7) in 3 patients receiving CsA and 1,998 micrograms ml-1 (s.d. 387) in 3 patients not receiving the drug. Clearance of antitumour antibody was accelerated and tumour localisation absent when HAMA levels exceeded 30 micrograms ml-1. With lower levels of HAMA in the CsA-treated patients, further antitumour antibody accumulated in the tumour after each dose. Further therapy with antitumour antibody and CsA lead to the development of HAMA, but this was less than 25% of the amount in patients not given CsA. In this preliminary study up to 4 times as many doses of antitumour antibody could be usefully given when CsA was used. This increases the potential for effective antibody targeted therapy of cancer.
Ledermann
J A
JA
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Begent
R H
RH
Bagshawe
K D
KD
Riggs
S J
SJ
Searle
F
F
Glaser
M G
MG
Green
A J
AJ
Dale
R G
RG
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D003131:Combined Modality Therapy; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003524:Cyclosporins; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes