Preclinical evaluation of immunoconjugates consisting of doxorubicin linked to complement-fixing monoclonal antibody DLC-48 for bone marrow purging of B-cell lymphomas.
Complement-fixing monoclonal antibody DLC-48 was linked covalently to doxorubicin using two methodologies, and the resulting conjugates were evaluated for their usefulness in purging B-cell lymphomas from human bone marrow autografts using a clonogenic assay for the large cell lymphoma cell line SU-DHL-4. Conjugation did not impair the reactivity of the antibodies. The resultant molar ratios provided for maximal immunoreactivity at doxorubicin concentrations that would permit the growth of CFU-GM. Conjugate DLC-48D-G retained its complement-fixing capacity, and was more cytotoxic to SU-DHL-4 cells, even in the absence of complement, than equivalent doses of doxorubicin. This effect appeared to be non-specific, in that CFU-GM were eliminated, even at low concentrations. DLC-48D-G was no more effective than equivalent doses of doxorubicin, and equally cytotoxic to CFU-GM. Mixtures of unconjugated DLC-48 and doxorubicin, however, were more effective than doxorubicin alone. The mechanism of action of these conjugates is under study. Alternative methods of conjugation will be investigated.
Winter
J N
JN
Department of Medicine, Northwestern University, Chicago, Illinois.
Bass
B
B
Bringman
T
T
Nedwin
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000276:immunology; D004317:Doxorubicin / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005455:Fluorescent Antibody Technique; D006801:Humans; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004317:Doxorubicin; D003165:Complement System Proteins