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 mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts.
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PMID:Imaging of human tumor xenografts with an indium-111-labeled anti-epidermal growth factor receptor monoclonal antibody. 279 90

Current treatment for late-stage metastatic breast cancer is largely palliative. alpha-Particles are highly potent, short-range radiation emissions capable of sterilizing individual cells with one to three traversals of the cell nucleus. The alpha-emitter, (213)Bi (T(1/2) = 45.6 min), was conjugated to a 100-nm diameter liposomal-CHX-A''-DTPA construct, upon which the rat HER2/neu reactive antibody, 7.16.4, was grafted. A conjugation time of 10 minutes was achieved giving a specific activity corresponding to 0.1 (213)Bi atom per liposome; stability in vitro and in vivo was confirmed. Efficacy in a rat/neu transgenic mouse model of metastatic mammary carcinoma was investigated. Three days after left cardiac ventricular injection of 10(5) rat HER-2/neu-expressing syngeneic tumor cells, macrophage-depleted Neu-N mice were treated by i.v. injection with (a) 19.2 MBq (520 muCi) of liposome-CHX-A''-DTPA-(213)Bi, (b) 19.2 MBq of liposome-CHX-A''-DTPA-(213)Bi-7.16.4, (c) 4.44 MBq (120 muCi) of (213)Bi-7.16.4, and (d) cold (nonradioactive) liposome-CHX-A''-DTPA-7.16.4 as control. Treatment with (a) increased median survival time to 34 days compared with 29 days for the untreated controls (P = 0.013) and 27 days for treated cold controls. Treatment with the radiolabeled antibody-conjugated liposome (b) increased median survival time to 38 days (P = 0.0002 relative to untreated controls). The radiolabeled antibody-treated group (c) gave a median survival of 39 days, which was similar to that for the radiolabeled antibody-conjugated liposome-treated group (P = 0.5). We have shown that the (213)Bi radiolabeled immunoliposomes are effective in treating early-stage micrometastases, giving median survival times similar to those obtained with antibody-mediated delivery of (213)Bi in this animal model.
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PMID:Immunoliposomal delivery of 213Bi for alpha-emitter targeting of metastatic breast cancer. 2065 Dec 54