Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin.
Results are presented showing the use of bispecific F(ab')2 antibodies (bsAbs) in the delivery of saporin for the treatment of 2 human B-cell malignancies. BsAbs delivering saporin through CD22, but not through CD19, were effective at inhibiting the uptake of [3H]leucine by Daudi and Raji cells. Furthermore, a combination of 2 anti-CD22 bsAbs, selected to bind simultaneously to saporin, bound saporin 20 times more avidly and inhibited protein synthesis far more efficiently than any single bsAb. In the first patient, with end-stage chronic lymphocytic leukaemia (CLL), treatment with 10 mg of saporin complexed to 100 mg of anti-CD19 bsAb over 43 days showed no therapeutic effect. In contrast, the second patient, with end-stage non-Hodgkin's lymphoma (NHL), given 5 mg of saporin complexed with a pair (50 mg) of anti-CD22 bsAbs over 15 days showed a marked clinical response, including complete clearance of tumour from the blood, clearance of ascites and shrinkage of tumour masses. Neither patient experienced any toxic side-effects, either during or after treatment. However, the second patient developed a strong anti-mouse Fab (HAMA) response 28 days after the treatment started. No anti-saporin response could be detected.
Bonardi
M A
MA
Lymphoma Research Unit, Southampton General Hospital, UK.
Bell
A
A
French
R R
RR
Gromo
G
G
Hamblin
T
T
Modena
D
D
Tutt
A L
AL
Glennie
M J
MJ
D000328:Adult; D000906:Antibodies / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins; D037102:Lectins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D051918:Sialic Acid Binding Ig-like Lectin 2
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; 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