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Vaccine Detail
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Ad5-yCD/mutTKSR39rep-hIL12 |
| Vaccine Information |
- Vaccine Name: Ad5-yCD/mutTKSR39rep-hIL12
- Target Pathogen: Cancer
- Target Disease: Cancer
- Vaccine Ontology ID: VO_0007572
- Type: Other
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Host Species as Laboratory Animal Model: Human
- IL12B
gene engineering:
- Type: Recombinant protein preparation
- Description:
- Detailed Gene Information: Click Here.
- IL12A
gene engineering:
- Type: Recombinant protein preparation
- Description:
- Detailed Gene Information: Click Here.
- Preparation: Adenoviruses were propagated in AD293 cells and purified by ion-exchange filtration (Freytag et al., 2013).
- Description: A replication-competent oncolytic adenovirus encoding the murine pro-inflammatory cytokine interleukin-12 (IL-12) gene and two suicide fusion genes, a yeast cytosine deaminase (yCD) and a mutant form of herpes simplex virus type 1 thymidine kinase (HSV-1 TKSR39), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration of Ad5-yCD/mutTKSR39rep-hIL12, the adenovirus selectively infects and replicates in tumor cells, which results in direct tumor cell lysis. Synergistically, IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and inducing cytotoxic T-lymphocyte (CTL) responses against tumor cells, which may result in immune-mediated tumor cell death, inhibition of tumor cell proliferation and inhibition of tumor angiogenesis. In addition, Ad5-yCD/mutTKSR39rep-hIL12-infected cancer cells (multiple types) express yCD and TKSR39; upon administration of the prodrugs 5-fluorocytosine (5-FC) and valganciclovir (vGCV), the yCD and HSV-1 TKSR39 activate these prodrugs to form 5-fluorouracil (5-FU) and ganciclovir, respectively. 5-FU gets converted to 5-fluoro-uridine monophosphate (5-FUMP) and subsequently to 5-fluoro-deoxyuridine monophosphate (5-FdUMP); 5-FdUMP irreversible inhibits thymidylate synthase, inhibits deoxythymidine triphosphate (dTTP) formation and halts DNA synthesis. Once phosphorylated intracellularly, ganciclovir triphosphate competitively inhibits deoxyguanosine triphosphate (dGTP) incorporation into DNA and inhibits DNA synthesis. (Barton et al., 2021; NCIT_C123930; Sato-Dahlman et al., 2020)
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| Host Response |
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| References |
Barton et al., 2021: Barton KN, Siddiqui F, Pompa R, Freytag SO, Khan G, Dobrosotskaya I, Ajlouni M, Zhang Y, Cheng J, Movsas B, Kwon D. Phase I trial of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for the treatment of metastatic pancreatic cancer. Molecular therapy oncolytics. 2021; 20; 94-9104. [PubMed: 33575474].
Freytag et al., 2013: Freytag SO, Barton KN, Zhang Y. Efficacy of oncolytic adenovirus expressing suicide genes and interleukin-12 in preclinical model of prostate cancer. Gene therapy. 2013; 20(12); 1131-1139. [PubMed: 23842593].
NCIT_C123930: [https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C123930]
Sato-Dahlman et al., 2020: Sato-Dahlman M, LaRocca CJ, Yanagiba C, Yamamoto M. Adenovirus and Immunotherapy: Advancing Cancer Treatment by Combination. Cancers. 2020; 12(5); . [PubMed: 32455560].
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