In vivo targeting of Hodgkin and Reed-Sternberg cells of Hodgkin's disease with monoclonal antibody Ber-H2 (CD30): immunohistological evidence.
The ability of the Ber-H2 (CD30) monoclonal antibody (mAb) to target in vivo Hodgkin (H) and Reed-Sternberg (R-S) cells was investigated in six patients with advanced Hodgkin's disease (HD). The patients were injected with scaled-up quantities of 'cold' Ber-H2 mixed-up to a small dose of 131I-labelled Ber-H2, and in vivo binding of the antibody to H and R-S cells was assessed by immunohistological analysis of tumour biopsies and immunoscintigraphy. Only 50% of tumour sites were imaged at scintigraphy by the 131I-labelled Ber-H2. In contrast, immunohistological studies on tissue biopsies, taken 24-72 h following the mAb injection, showed that H and R-S cells in all tumour sites, including those that were not imaged by immunoscintigraphy, were specifically and strongly labelled in vivo by the injected Ber-H2, at a dose as low as 30-50 mg of antibody. In vivo binding of a single dose of Ber-H2 mAb to H and R-S cells did not result in any anti-tumour effect. The excellent in vivo targeting of H and R-S cells with the Ber-H2 mAb may have been the result of multiple favourable factors, including: (a) the restricted expression of the CD30 antigen in normal human tissues; (b) the low level of soluble CD30 in the serum of our patients; and (c) the high affinity of the Ber-H2 mAb for the CD30 molecule. The immunohistological results presented in this study provide a strong argument for using the Ber-H2 mAb as a carrier for delivering cytotoxic agents (isotopes or toxins) to neoplastic cells of HD refractory to conventional therapy.
Falini
B
B
Institute of Haematology, University of Perugia, Italy.
Flenghi
L
L
Fedeli
L
L
Broe
M K
MK
Bonino
C
C
Stein
H
H
Dürkop
H
H
Bigerna
B
B
Barbabietola
G
G
Venturi
S
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017730:Ki-1 Antigen; D008297:Male; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000276:immunology*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D017730:Ki-1 Antigen