Immunotherapy with monoclonal anti-idiotypic antibodies: tumour reduction and lymphokine production.
A patient with a B-cell chronic lymphocytic leukaemia was treated with a murine IgG1 monoclonal anti-idiotypic antibody (MoAb anti-id). After a total of 773.2 mg MoAb anti-id had been administered with a maximum daily dose of 83.2 mg, 90% tumour reduction was established within 2 weeks. Although in vitro the tumour cells were stimulated by MoAb anti-id no signs of tumour cell activation were observed in vivo during therapy with MoAb anti-id. The rapid tumour reduction suggests that the proliferation-enhancing property of anti-id is not a contra-indication for immunotherapy. The FcR II receptors on the patients monocytes could interact with the IgG1 monoclonal used. MoAb anti-id administration induced strongly decreased platelet counts, dependent on the amount of serum idiotype that had to be cleared. Antibody administration activated the macrophage/monocyte system, reflected in the neopterin profile, resulting in TNF alpha production and simultaneously strong reductions of circulating tumour cells. The partial remission lasted 3 months, then the tumour reappeared. These data show that a straightforward therapy with MoAb anti-id, in itself, has a strong potential, but is not sufficient to eradicate the tumour permanently. Further study will be needed to improve the clinical results with this kind of therapy.
Allebes
W
W
Department of Nephrology, University Hospital, Nijmegen, The Netherlands.
Knops
R
R
Herold
M
M
Huber
C
C
Haanen
C
C
Capel
P
P
D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001708:Biopterins / Q000031:analogs & derivatives / Q000096:biosynthesis; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*; D008222:Lymphokines / Q000096:biosynthesis*; D008262:Macrophage Activation; D019798:Neopterin; D011961:Receptors, Fc / Q000378:metabolism; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D008222:Lymphokines; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D003165:Complement System Proteins