Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fields of radioimmunodetection and radioimmunotherapy began with an initial paradigm that a targeting molecule (eg, antibody) carrying a radioisotope had the potential of selectively imaging and delivering a therapeutic dose of radiation to tumor sites. A second paradigm was developed in which injection of the targeting molecule was separated from injection of a short-lived radioisotope-labeled ligand (so-called "pretargeting strategy"). This strategy has improved radioisotope delivery to tumors in animal models, enhanced radioimmune imaging in man, and therapeutic trials are in an early phase. We proposed a third paradigm to achieve radioisotopic localization at tumor sites by inducing tumor cells to synthesize a membrane expressed receptor with a high affinity for infused radiolabeled ligands. The use of gene transfer technology to induce expression of high affinity membrane receptors can enhance the specificity of radioligand localization, while the use of radioisotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency. This approach was termed "Genetic Radioisotope Targeting Strategy." Using this strategy, induction of high levels of gastrin releasing peptide receptor or human somatostatin receptor subtype 2 expression and selective tumor uptake of radiolabeled peptides was achieved. The advantages of the genetic transduction approach are (1) constitutive expression of a tumor-associated antigen/receptor is not required; (2) tumor cells are altered to express a new target receptor or increased quantities of an existing receptor at levels that may significantly improve tumor targeting of radiolabeled ligands compared with normal tissues; (3) gene transfer can be achieved by intratumoral or regional injection of gene vectors; (4) it is feasible to target adenovirus vectors to receptors overexpressed on tumor cells by modifying adenoviral tropism (binding) so that the virus will be targeted specifically to the desired tumor; and (5) it is possible to coexpress the receptor gene and a therapeutic gene, such as cytosine deaminase, for molecular prodrug therapy to produce an enhanced therapeutic effect.
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PMID:Imaging and therapy of tumors induced to express somatostatin receptor by gene transfer using radiolabeled peptides and single chain antibody constructs. 1473 57

S.c. injection of the Ad-sig-tumor-associated antigen (TAA)/ecdCD40L vector vaccine has been shown to induce a CD8 immune response against TAA for up to 1 year. The first goal of this article is to test if the injection of autologous dendritic cells infected ex vivo with the Ad-sig-TAA/ecdCD40L can increase the immune response induced against TAA. The second goal is to test the effect of adding local chemotherapy in the form of i.t. injection of the AdCDIRESE1A vector-directed chemotherapy on the immune response induced by i.t. injection of adenoviral vector-activated dendritic cells. The results show that the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector, which encodes the cytosine deaminase chemotherapy sensitization transcription unit, to the i.t. injection of Ad-sig-ecdCD40L vector-infected dendritic cells increased the level of suppression of the growth of the CCL-51 breast cancer cells. The combination of i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector and Ad-sig-ecdCD40L vector-infected dendritic cells into s.c. CCL-51 breast cancer nodules suppressed the growth of uninjected metastatic tumor nodules in the lung. Finally, adding the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector to the i.t. administration of dendritic cells infected with a rat HER-2/neu (rH2N)-expressing vector (Ad-sig-rH2N/ecdCD40L) led to the induction of rH2N-specific antitumoral immunity in rH2N transgenic mice (which are anergic to the rH2N antigen). This anti-rH2N immune response suppressed the growth of established H2N-positive NT2 breast cancer more efficiently than did the vector-targeted chemotherapy or Ad-sig-rH2N/ecdCD40L-infected dendritic cell vaccine alone.
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PMID:Antitumor immune response induced by i.t. injection of vector-activated dendritic cells and chemotherapy suppresses metastatic breast cancer. 1692 18