Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy. Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach. Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies. Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells. These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.
 ...
PMID:Targeting strategy for gene delivery to carcinoembryonic antigen-producing cancer cells by retrovirus displaying a single-chain variable fragment antibody. 947 83

Activation of cytotoxic T cells without MHC restriction was attempted by expressing single-chain antibodies (scFv) against CD3 on the surface of tumor cells. A chimeric protein consisting of a scFv of mAb 145.2C11, the hinge-CH2-CH3 region of human IgG1, and the transmembrane and cytosolic domains of murine CD80 formed disulfide-linked dimers on the plasma membrane of cells and specifically bound lymphocytes. Anti-CD3 scFv dimers expressed on the cell surface induced CD25 (IL-2 receptor alpha-chain) expression and proliferation of splenocytes. CT26 tumor cells engineered to express surface scFv dimers (CT26/2C11) also induced potent lymphocyte cytotoxicity with or without addition of exogenous IL-2. Splenocytes activated by CT26/2C11 cells also killed wild-type CT26 cells, indicating that activated splenocytes could kill bystander tumor cells. Immunization of BALB/c mice with irradiated CT26/2C11 cells did not protect against a lethal challenge of CT26 cells, suggesting that systemic immunity was not induced. However, the growth of CT26 tumors containing 50% CT26/2C11 cells was significantly retarded compared with CT26 tumors, whereas CT26/2C11 tumors did not grow in syngeneic mice. These results suggest that expression of anti-CD3 scFv dimers on tumors may form the basis for a novel therapeutic strategy for tumors that exhibit defects in antigen processing or presentation. Gene Therapy (2000) 7, 339-347.
 ...
PMID:Activation of lymphocytes by anti-CD3 single-chain antibody dimers expressed on the plasma membrane of tumor cells. 1069 15

Self-assembled particles of genetically engineered human L subunit ferritin expressing a silver-binding peptide were used as nanocontainers for the synthesis of silver nanoparticles. The inner cavity of the self-assembled protein cage displays a dodecapeptide that is capable of reducing silver ions to metallic silver. This chimeric protein cage when incubated in the presence of silver nitrate exhibits the growth of a silver nanocrystal within its cavity. Our studies indicate that it is possible to design chimeric cages, using specific peptide templates, for the growth of other inorganic nanoparticles.
 ...
PMID:Engineered protein cages for nanomaterial synthesis. 1547 82

In addition to its role in cancer, the c-Myc oncoprotein controls many normal cellular processes as a consequence of its function as a basic helix-loop-helix leucine zipper transcription factor. Determining which of the myriad genes under c-Myc control are relevant for these various roles is thus a major challenge. mt-mc1 is a direct c-Myc target gene whose overexpression recapitulates multiple c-Myc phenotypes, including transformation. Using transcriptional profiling, we now show that MT-MC1-overexpressing myeloid cells misregulate a total of 47 distinct transcripts, a large proportion of which are involved in signal transduction and/or cancer. Analysis of these genes reveals a consensus promoter structure consisting of multiple, often closely spaced c-Myc binding sites and three additional Wilm's tumor and Egr1-like motifs. More than one-third of MT-MC1 target genes are also clustered on six cancer-associated chromosomal loci. Most surprisingly, all of the transcripts examined also are regulated by c-Myc. Finally, an estrogen receptor-MT-MC1 fusion protein was used to establish that all examined transcripts were regulated directly by the chimeric protein. Our results thus indicate that MT-MC1 target genes largely comprise a subset of those regulated by c-Myc. We propose that the properties imparted by MT-MC1 are the result of its control of a small and select c-Myc target gene population.
 ...
PMID:Deregulation of common genes by c-Myc and its direct target, MT-MC1. 1636 99

Artificially enforced expression of CD80 (B7-1) and CD86 (B7-2) on tumor cells renders them more immunogenic by triggering the CD28 receptor on T cells. The enigma is that such B7s interact with much higher affinity with CTLA-4 (CD152), an inhibitory receptor expressed by activated T cells. We show that unmutated CD80 is spontaneously expressed at low levels by mouse colon carcinoma cell lines and other transplantable tumor cell lines of various tissue origins. Silencing of CD80 by interfering RNA led to loss of tumorigenicity of CT26 colon carcinoma in immunocompetent mice, but not in immunodeficient Rag-/- mice. CT26 tumor cells bind CTLA-4Ig, but much more faintly with a similar CD28Ig chimeric protein, thus providing an explanation for the dominant inhibitory effects on tumor immunity displayed by CD80 at that expression level. Interestingly, CD80-negative tumor cell lines such as MC38 colon carcinoma and B16 melanoma express CD80 at dim levels during in vivo growth in syngeneic mice. Therefore, low CD80 surface expression seems to give an advantage to cancer cells against the immune system. Our findings are similar with the inhibitory role described for the dim CD80 expression on immature dendritic cells, providing an explanation for the low levels of CD80 expression described in various human malignancies.
 ...
PMID:Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma. 1648 51

Human ferritins have been extensively studied to be used as nanocarriers for diverse applications and could represent a convenient alternative for targeted delivery of anticancer drugs and imaging agents. However, the most relevant limitation to their applications is the need for highly acidic experimental conditions during the initial steps of particle/cargo assembly, a process that could affect both drug stability and the complete reassembly of the ferritin cage. To overcome this issue the unique assembly of Archaeoglobus fulgidus ferritin was genetically engineered by changing a surface exposed loop of 12 amino acids connecting B and C helices to mimic the sequence of the analogous human H-chain ferritin loop. This new chimeric protein was shown to maintain the unique, cation linked, association-dissociation properties of Archaeoglobus fulgidus ferritin occurring at neutral pH values, while exhibiting the typical human H-homopolymer recognition by the transferrin receptor TfR1. The chimeric protein was confirmed to be actively and specifically internalized by HeLa cells, thus representing a unique nanotechnological tool for cell-targeted delivery of possible payloads for diagnostic or therapeutic purposes. Moreover, it was demonstrated that the 12 amino acids' loop is necessary and sufficient for binding to the transferrin receptor. The three-dimensional structure of the humanized Archaeoglobus ferritin has been obtained both as crystals by X-ray diffraction and in solution by cryo-EM.
 ...
PMID:Humanized archaeal ferritin as a tool for cell targeted delivery. 2794 79