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.
Department of Medicine, Northwestern University, Chicago, Illinois.
J N
JN
Winter
B
B
Bass
T
T
Bringman
G
G
Nedwin
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