| 摘要 |
Immunogens, immunogenic compositions and a method for the detection and treatment of gastrin-dependent tumours are discussed. The immunogens comprise a natural or synthetic peptide from the gastrin/cholecystokinin (CCK)-B receptor conjugated to a spacer amino acid sequence and an immunogenic protein carrier, such as diphtheria toxoid, tetanus toxoid, or bovine serum albumin. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin receptors on tumour cells, thereby preventing growth stimulating peptide hormones from binding to the receptors and thereby inhibiting tumour cell growth. Methods of immunization against the CCK-B/gastrin receptor include active and passive immunization. For active immunisation, a patient is immunized with an immunogen. The immunogen stimulates the production of antibodies against the CCK-B/gastrin receptor on tumour cells. The antibodies are specific to the NH2-terminal end of the receptor and upon binding are internalised and rapidly translocated into the cytoplasm and into the nucleus of the tumour cells. This rapid internalisation of the antibody/receptor complex in turn causes the affected tumour cells to undergo apoptosis or suicide. For passive immunization, the antibodies against the CCK-B/gastrin receptor are administered to a patient in a sufficient concentration to bind to the CCK-B/gastrin receptors of the tumour cells and the antibodies block the binding of the peptide hormones to the receptor. Preventing binding of the hormones to their receptor inhibits the growth-stimulus pathway of the tumour cells, thereby inhibiting the growth of the hormone-dependent tumours. The antibodies for human therapy may be chimeric, humanized, or human monoclonal antibodies which are produced by known methods. The anti-CCK-B/gastrin receptor antibodies may be further conjugated to cytotoxic molecules such as cholera toxin, or to molecules labelled with radioactive molecules, such as isotopes 125I and 131I, to enhance the killing of the tumour cells.
|
