Response of B-cell lymphoma to a combination of bispecific antibodies and saporin.
Observations are described using a combination of two bispecific F(ab')2 antibodies (BsAb) to deliver the ribosome-inactivating protein, saporin, in the treatment of low-grade, end-stage, B-cell lymphoma. Two BsAb were used, each having one arm directed at saporin and one at the CD22 on target B cells. The BsAb, however, recognized different, non-overlapping epitopes on each molecule, a strategy which permits high-avidity double attachment of saporin to the target. The BsAb and saporin were pre-mixed at a molar ratio of 3:1 24 h before treatment and infused intravenously over a period of 1 h. Five patients have been treated, mostly with weekly doses of between 2 and 4 mg of saporin for a period of up to 6 weeks. Toxicity was minimal. Three complained of weakness and myalgia for 1 to 2 days after treatment, without objective neurological deficit or rise in serum creatine kinase. One patient produced an anti-mouse Fab' and an anti-saporin response. All patients showed a rapid and beneficial response to treatment. When present, circulating tumor cells were cleared (4/4 patients), ascitic and pleural effusions were eliminated (2/2 patients) and one patient with splenomegaly showed a marked reduction in tumor bulk. Malignant lymph nodes showed significant, but partial, shrinkage in all patients and finally marrow responded well with tumor clearance in biopsy material and impressive resolution of pancytopenia in some patients. While these responses were mainly short-lived, with tumor progression once the treatment was stopped, their speed and magnitude, and the relative lack of associated toxicity warrants further study of this treatment to determine maximum tolerated doses and therapeutic utility.
French
R R
RR
Lymphoma Research Unit, Tenovus Research Laboratory, Southampton General Hospital, U.K.
Bell
A J
AJ
Hamblin
T J
TJ
Tutt
A L
AL
Glennie
M J
MJ
D000368:Aged; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D016130:Immunophenotyping; D000922:Immunotoxins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D037102:Lectins; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D051918:Sialic Acid Binding Ig-like Lectin 2; D013154:Spleen / Q000000981:diagnostic imaging / Q000276:immunology; D014057:Tomography, X-Ray Computed
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D037102:Lectins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D051918:Sialic Acid Binding Ig-like Lectin 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins