Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin.
A retrospective study was performed in order to examine the clinical relevance of human anti-murine antibodies (HAMA) to concurrent clinical events in 21 patients receiving intravenous therapy with cocktails of murine monoclonal antibodies conjugated to Adriamycin. In vivo tumor localization of the murine antibodies was also evaluated. Serum levels of HAMA, human-murine immune complexes (HMIC), and murine antibodies were measured using an automated fluorescence immunoassay. Immunohistochemical staining was performed on frozen sections of tumor biopsies from eight of the patients to examine the in vivo binding of the murine antibodies. The patients were divided into low, intermediate, and high antibody dose groups. The incidence of allergic symptoms (80%) and HAMA correlation (75%) were highest in the low dose group. Specific IgM HAMA was the most highly correlated with allergic reactions, being present in 61.5% of the allergic patients. Thirteen of the 21 patients studied (61.9%) developed allergic symptoms after one or more doses of the murine monoclonal antibody conjugates. The percentages of total antibody doses in the patients' sera at varying intervals post-infusion varied widely from patient to patient for any given time point and dose, suggesting complex factors in the distribution and clearance of the murine antibodies. All eight of the patients biopsied during or post-therapy exhibited tumor localization of the murine monoclonal antibodies. Six of the eight had concurrent HAMA in their sera. Thus, the presence of HAMA did not prevent in vivo localization of the murine antibodies in the target tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Avner
B
B
Biotherapeutics Associates Inc., Plantation, FL.
Swindell
L
L
Sharp
E
E
Liao
S K
SK
Ogden
J R
JR
Avner
B P
BP
Oldham
R K
RK
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000097:blood; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D007167:Immunotherapy / Q000009:adverse effects; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D004317:Doxorubicin