Treatment of cutaneous T-cell lymphoma with chimeric anti-CD4 monoclonal antibody.
Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.
Knox
S
S
Department of Radiation Oncology, Stanford University School of Medicine, CA, USA.
Hoppe
R T
RT
Maloney
D
D
Gibbs
I
I
Fowler
S
S
Marquez
C
C
Cornbleet
P J
PJ
Levy
R
R
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007121:Immunocompetence; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D011994:Recombinant Proteins