Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunogenicity of the idiotypic portions of two antigrowth factor receptor monoclonal antibodies (MAbs) was studied. Immunisation of allogeneic but not syngeneic mice with antihuman epidermal growth factor receptor (EGF-R) MAb MINT5 or anti-HER-2/neu MGR6 MAb elicited a detectable titre of circulating antibodies, particularly when the MAb was coupled with the keyhole limpet haemocyanin and administered together with Freund's adjuvant. The anti-Ab1 response to MAb MINT5 was slightly delayed as compared with the response obtained with MAb MGR6 and was mainly directed to the variable regions. In both cases, all anti-Ab1-positive sera specifically competed with the binding of homologous radiolabelled Ab1 to the relevant EGF-R+ or HER-2/neu+ target cells. Fusion of splenocytes from MINT5-immunised animals failed to produce MAb, whereas cell fusion was successful in generating a paratope-related MAb in the case of MGR6. The anti-MGR6 MAb-produced IdM6.4 inhibited the binding of MAb MGR6 on breast carcinoma cells, suggesting that it recognises an idiotope in or near the antigen combining site, and can be considered useful in the identification and purification of the Ab1 or its derivatives. We analysed whether a possible recognition of murine EGF-R by MAb MINT5 or a mimicry of EGF by the MAb idiotype prevented or delayed the development of an idiotypic cascade in mice. MINT5 inhibited human and murine EGF binding to the human EGF-R, whereas the anti-Ab1 response competed with MINT5 but not with murine EGF binding to A431 human epidermoid carcinoma cells. Moreover, MINT5 did not recognise the murine EGF-R. In a phase I clinical study, no detectable levels of human antimouse antibody response were observed in 5 of the 6 treated cancer patients. The ability of MAb MINT5 to block human EGF-R function, together with its low immunogenicity in patients, raise the possibility of its application in carcinoma immunotherapy.
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PMID:Anti-idiotypic response to antigrowth factor receptor monoclonal antibodies. 881 98

Morphologic mimicry among human malignant neoplasms is a well-known phenomenon in surgical pathology; both undifferentiated and "committed" neoplasms may exhibit this trait. One particularly common group of histologic simulants includes ductal carcinomas of the breasts, the cutaneous appendages, and the salivary glands. One hundred three tumors in this structural cluster were analyzed microscopically and immunohistologically to codify points of potential pathologic similarity and difference. All the lesions were typified by irregularly permeative clusters and cords of atypical polygonal cells with variable luminal differentiation. A proportion of primary neoplasms in each site demonstrated in situ ductal components; in the absence of the latter elements, however, it was not possible to make topography-related morphologic distinctions among them. Immunostains for gross cystic disease fluid protein-15 (GCDFP-15), carcinoembryonic antigen, S100 protein, c-erbB-2 oncoprotein, estrogen receptor protein, and progesterone receptor protein also showed largely overlapping phenotypes in each of the three tumor categories, with selected exceptions. These differences were elucidated through paired chi 2 analysis and included a statistically significant infrequency of GCDFP-15 in eccrine sweat gland carcinomas, a paucity of carcinoembryonic antigen in breast cancers, and an absence of estrogen receptor protein in salivary duct carcinomas. Such findings may be useful in predefined differential diagnostic settings involving the distinction between primary and metastatic ductal cancers of the breasts, skin, and salivary glands. Nevertheless, because of the striking homologies between such tumors at structural and protein-synthetic levels of comparison, it is mandatory that all available clinicopathologic information be used in this context.
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PMID:Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma. 1023 Mar 63

Cancer vaccines have been explored clinically against melanomas, adenocarcinomas and lymphomas. Breast cancer vaccines include Theratope, MUC1 mucin peptides and HER-2/neu peptide vaccines. Phase II trials suggest prolongation of survival of advanced breast cancer patients who generate high titers of antibody to Theratope. In contrast, melanoma ganglioside vaccines, which also elicit only antibodies, have not been effective in improving survival in controlled trials. Anti-idiotype vaccines for solid tumors, which depend upon mimicry of the tumor-associated antigens, have also had limited success. In lymphomas, where the idiotypes are the tumor-associated antigens, greater success has been achieved. A number of tumor-associated antigens have been identified in melanoma, such as the lineage related cancer-testis group (MAGE) and tyrosinase-related antigens. Non-lineage related antigens shared among a variety of very different tumors have recently been demonstrated too, which may permit immunization against more than one tumor group. Telomerase and MG50, one of several interleukin-1 receptor antagonist molecules, are both immunogenic and widespread in their representation. Carcinoembryonic antigen is the basis for vaccines against many adenocarcinomas. Both viral and non-viral vectors are being used to improve the reactivity to peptides in adenocarcinomas. Dendritic cell-carried vaccines, which package the antigens ex vivo rather than depending upon in vivo uptake, are being extensively explored in clinical models to improve the effectiveness of defined vaccines, such as peptides and RNA. 'Naked' DNA vaccines injected intramuscularly also have their advocates. Among the most recent attempts to improve the immunogenicity of vaccines is the use of antigens newly identified by genomic techniques and 'superagonist' peptide mimics, selected from combinatorial peptide libraries. These modern biochemical and molecular biological methods may greatly expand our ability to immunize against tumor antigens, which are essentially 'self' molecules. Finally, a greater understanding of ways in which tumors escape immunological detection or thwart immunological responses should lead to improved strategies against the tumor to augment the effect of vaccination.
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PMID:Cancer vaccines, a critical review--Part II. 1205 66