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1.
Clin Cancer Res ; 6(12): 4674-83, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11156219

RESUMO

The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1kappa) antibody was secreted from Chinese hamster ovary cells and purified by a multistep chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Biodistribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2 level the half-life and maximum serum concentration were 81 +/- 15 h and 7.9 microg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Adulto , Idoso , Animais , Anticorpos Monoclonais/efeitos adversos , Células CHO , Cromatografia , Cromatografia em Gel , Cricetinae , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Radioisótopos do Iodo/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Fatores de Tempo , Tomografia Computadorizada de Emissão , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
J Clin Immunol ; 17(6): 502-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9418191

RESUMO

Proteins with glycosylphosphatidylinositol (GPI) anchors exhibit a range of activities and some of these proteins exist in both a membrane-associated and a soluble form. CD48 is a 47-kd GPI-linked glycoprotein which is expressed on T and B lymphocytes, monocytes, and many lymphoid malignancies. The biological function of CD48 is unknown. We describe the detection of a soluble form of CD48 in plasma and serum. Its level was quantified by an immunoenzymometric assay (IEMA) specific for soluble CD48. While soluble CD48 was detected in the plasma of healthy individuals (median = 29 ng/ml; range, 15-48 ng/ml), elevated levels were detected in some patients with lymphoproliferative disease (median = 41 ng/ml; range, 9-213 ng/ml, arthritis (median = 42 ng/ml; range, 13-67 ng/ml), and acute EBV infection (174 ng/ml). Soluble CD48 was also detectable in tissue culture supernatants from the Raji lymphoid cell line. The mechanism of CD48 release from cells is unclear. The finding of significant levels of soluble CD48 in plasma and the development of a sensitive IEMA for its measurement will facilitate further studies on its normal function and its role in disease.


Assuntos
Antígenos CD/sangue , Antígenos de Superfície/sangue , Artrite/sangue , Leucemia Linfoide/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/análise , Antígenos CD/imunologia , Antígeno CD48 , Linhagem Celular , Feminino , Citometria de Fluxo , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/fisiopatologia , Herpesvirus Humano 4/imunologia , Humanos , Imunoensaio , Leucemia Linfocítica Crônica de Células B/sangue , Leucócitos/imunologia , Leucócitos Mononucleares/química , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Linfoma não Hodgkin/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Nus , Pessoa de Meia-Idade , Dados de Sequência Molecular , Sensibilidade e Especificidade
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