Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carcinoembryonic antigen (CEA) is expressed at greatly increased levels in nearly all human colorectal carcinomas. Anti-CEA antibodies have been proved to be useful for targeting several cancer types known to express CEA. A recombinant immunotoxin was constructed, in which the cell-binding domain of Pseudomonas exotoxin (PE) was replaced with the single-chain Fv (scFv) of anti-CEA monoclonal antibody for targeting to colorectal carcinomas. This single-chain immunotoxin was expressed in E. coli and purified under denaturing condition of 6M guanidine hydrochloride (GuHCl). It was found that the immunotoxin maintains a binding activity in denaturing condition of 6M GuHCl and the fused PE contributes to the stability of immunotoxin in such condition. Dialysis against PBS buffer after purification under 6M GuHCl keeps the binding activity of immunotoxin.
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PMID:Expression and purification of recombinant immunotoxin--a fusion protein stabilizes a single-chain Fv (scFv) in denaturing condition. 1250 88

Carcinoembryonic antigen (CEA) is expressed in approximately 60% of breast carcinomas. T84.66 is a well characterized anti-CEA murine monoclonal antibody (MAb) that does not cross-react with other CEA-related proteins. It has been humanized and used extensively after radiolabeling in clinical/experimental protocols for localization/therapy of colorectal cancer. MCF-7 human breast cancer cell line expresses CEA and is tumorigenic in athymic mice. In order to determine if anti-CEA MAb could specifically target breast cancer CEA, biodistribution, radiolocalization and therapy studies were performed in the animal model. Five tumor-bearing animals per time point were injected with 15 muCi of In-111-cT84.66. Mice were imaged and sacrificed at 24, 48, 72 and 144 h and biodistribution studies performed. For therapy studies, 19 tumor-bearing mice were injected either with 120 muCi of 90Y-cT84.66 or PBS. The tumors were measured tri-weekly and weighed at autopsy 21 days post therapy. Activity accumulation steadily increased in the tumors reaching 21% of the injected dose per gram of tumor (ID/g) at 144 h. At that time, the %ID/g in the tumor was 3 times higher than that in blood and the liver and 8 times higher than in other major organs. On day 10 post-therapy, 16 of the 19 control mice had tumor volumes between 1 and 3 cm3, while none of the treated tumors ever reached 1 cm3 in size. At autopsy, a 12-fold tumor weight difference (p=0.0001) was observed between control and treated mice (2.4g vs. 0.2g average weight, respectively). In summary, breast cancer CEA was specifically targeted with T84.66 allowing good tumor localization as well as significant tumor growth inhibition. Given the significant expression of CEA in breast cancer, this tumor should be included into the CEA-expressing malignancies for targeting with anti-CEA MAbs.
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PMID:Breast-tumor xenograft targeting and therapy studies using radiolabeled chimeric anti-cea monoclonal-antibody t84.66. 2159 19

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8+ T cells, as depletion of circulating CD8+ T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.
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PMID:A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer. 2902 49