Low incidence of antibodies to recombinant human tissue-type plasminogen activator in treated patients.
Sera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients' serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.
Reed
B R
BR
Department of Medicinal and Analytical Chemistry, Genentech, Inc., South San Francisco 94080.
Chen
A B
AB
Tanswell
P
P
Prince
W S
WS
Wert
R M
RM
Glaesle-Schwarz
L
L
Grossbard
E B
EB
D000818:Animals; D000906:Antibodies / Q000097:blood*; D002143:Callitrichinae; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D006801:Humans; D015531:Radioimmunoprecipitation Assay; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000276:immunology* / Q000627:therapeutic use
D000906:Antibodies; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator