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Vladimir Prokhorov
Vladimir Prokhorov

Buy Oncept Vaccine


The protocol for direct treatment of lesions calls for administering four injections bi-weekly and then twice more monthly. In the study researchers administered the vaccine directly into the tumor using a disposable CO2-powered, needleless injector. They injected a single shot of DNA plasmid material under pressure to get the DNA through cell membranes, where it is taken up within the interstitial spaces (between cells). Once the antigen is present, says Lawman, T-cells kill the tumor locally while also eliciting a systemic response to kill cancer in noninjected tumors elsewhere on the body.




buy oncept vaccine



Availability of the canine vaccine is limited to board-certified small animal internal medicine and oncology specialists. Availability to equine veterinarians will be determined later if the vaccine receives approval.


While a large percentage of gray horses over the age of 15 develop localized cutaneous melanoma lesions, many tend to be cosmetic in nature. However, invasive malignant melanoma does occur. Metastases, or secondary growth at distances from the primary tumor, to internal structures such as salivary glands, the gastrointestinal tract, and the guttural pouch might cause weight loss, colic, neurologic conditions, or difficulty defecating. New research is revealing more options to target melanoma cancer cells to control tumor growth and advancement. While scientists are still in the investigative process, our sources say vaccine technology that relies on cloning DNA genes into molecular vectors shows promise for managing equine melanoma.


Canine Melanoma Vaccine, DNA (Trade name: Oncept) consists of highly purified plasmid DNA capable of expressing the human tyrosinase protein in transfected canine cells. The product is a therapeutic vaccine to be administered to dogs with stage II or stage III oral melanoma to aid in extending survival times. The vaccine was evaluated by the Canadian Centre for Veterinary Biologics of the Canadian Food Inspection Agency for licensing in Canada. As part of the requirements for licensing this product in Canada, an "Environmental Assessment" was conducted, and a public document containing information on the molecular and biological characteristics of the genetically modified organism, target animal and non-target animal safety, human safety, environmental considerations, and risk-mitigating measures was prepared.


The Canadian Centre for Veterinary Biologics (CCVB) of the Canadian Food Inspection Agency (CFIA) is responsible for licensing veterinary biologics for use in Canada. The legal authority for the regulation of veterinary biologics in Canada is provided under the Health of Animals Act and the Health of Animals Regulations. Any veterinary biologic manufactured, sold, or represented for use in Canada must comply with the requirements specified by the CFIA regarding the safety, purity, potency, and efficacy of the product. Merial Inc. (Athens, Georgia, USA) through Merial Canada Inc. (Baie d'Urfé, Quebec) has submitted the following vaccine for licensing in Canada:


Canine Melanoma Vaccine, DNA, is an unadjuvanted vaccine consisting of highly purified plasmid DNA. Following uptake by canine cells near the injection site, a gene encoding the human tyrosinase protein is expressed from the plasmid, using host cellular machinery. This vaccine-derived xenogeneic immunogen is then detected by the vaccinee's immune system, leading to both humoral and cell-mediated immune responses. Vaccination with human tyrosinase appears to break tolerance for the related self canine tyrosinase protein, and an immune response against the endogenous canine tyrosinase expressed by the melanoma cells is mounted. The plasmid is non-replicating in eukaryotic cells.


The CCVB evaluates veterinary biologic product submissions for licensure under the Health of Animals Act and the Health of Animals Regulations. The general criteria for licensing are as follows: a) the product must be pure, safe, potent, and efficacious; b) vaccine components must be relevant to Canadian disease conditions; c) foreign products must be licensed in the country of origin; and d) the product must be produced and tested in accordance with generally accepted "good manufacturing practices." This U.S.-origin vaccine meets these general criteria, and presents no unacceptable importation risk, and thus was evaluated for licensing by the CCVB.


The vaccine is not an organism but a double-stranded, covalently closed, circular DNA molecule known as a plasmid. The plasmid is propagated for vaccine production in an E. coli host strain commonly used in laboratories. The vaccine plasmid is unable to replicate autonomously in a eukaryotic host cell.


The vaccine plasmid contains an origin of replication, a gene-conferring antibiotic resistance, and complementary DNA (cDNA), encoding human tyrosinase under the control of a viral immediate-early promoter/enhancer and a transcription termination sequence.


The origin of replication sequence allows the vaccine plasmid to be replicated within the E. coli cells cultured for vaccine production. The antibiotic resistance gene facilitates the selection of bacteria carrying the plasmid and the propagation of only those E. coli containing the vaccine plasmid during vaccine manufacturing. The antibiotic resistance gene is under the control of prokaryotic regulatory sequences, and is oriented in the opposite direction to the promoter-controlling tyrosinase expression, so it should not be expressed in eukaryotic cells. The human tyrosinase cDNA encodes the vaccine antigen, and the viral promoter plus the terminator sequences drive the expression of the antigen in dog cells following vaccination.


The cDNA encoding human tyrosinase sequence (approximately two kilo-base pairs in length) was obtained from a cDNA library prepared from a human melanoma cell line. The other functional elements of the vaccine plasmid correspond to sequences present in numerous commercially available plasmids.


Each batch (serial) of Canine Melanoma Vaccine, DNA, is tested for its continued ability to express the human tyrosinase antigen in a mammalian cell line. Restriction enzyme (RE) digests are also performed on each batch of the final vaccine to ensure that the RE profile is as expected and that no gross rearrangements (e.g. deletions, duplications) occurred to alter the predominant plasmid population. After establishing a master cell bank (MCB), which serves as the starting material for each batch of Canine Melanoma Vaccine, DNA, the manufacturer sequenced the entire plasmid isolated from a first passage culture and found that the sequence was 100% as expected.


The serial employed in the efficacy studies used to support product licensing was produced by isolating plasmid DNA from a culture at the maximum number of passages from the MCB permitted during the production of a vaccine serial.


The presence of an antibiotic resistance gene on the vaccine plasmid leads to the question of whether the plasmid is likely to participate in horizontal gene transfer (HGT). The vaccine will be delivered into the dermal and/or muscle tissues of dogs, where there should be no bacteria capable of propagating the plasmid. For intact plasmid DNA to reach bacteria making up the natural gut flora of the vaccinee, it will have to evade degradation by nucleases present in the extracellular space and blood, cross the intestinal barrier, and then survive degradation by nucleases present in the intestines. Accomplishing this feat, a bacterium then needs to take up the plasmid by DNA transformation, which is an inefficient process and a rare event outside of optimized laboratory conditions. It could be envisioned that a small amount of plasmid DNA could be exuded from the site of vaccine injection and licked by the dog as a minor source of oral exposure. Here, the likelihood of HGT to bacteria in the mouth is also minimal, due to the inefficiency of bacterial transformation of naked DNA and the presence of nucleases in saliva. In both the aforementioned cases, the chances of stable HGT are further reduced by the fact that bacteria transformed with the vaccine plasmid are unlikely to retain the plasmid in the absence of the appropriate antibiotic selection pressure. Taken together, there are many barriers that should restrict the chances of the vaccine plasmid participating in a HGT event. Since the antibiotic against which the vaccine plasmid's antibiotic resistance gene confers resistance is currently of limited therapeutic value in veterinary and human medicine, the impact of a rare HGT event would also be relatively minor.


It should be noted that antibiotic resistance genes, similar or identical to that present on the vaccine plasmid, are frequently found on plasmids used in research, in soil bacteria, and in transgenic plants approved for use in Canada as food and/or feed crops (Miki and McHugh, 2004). Use of Canine Melanoma Vaccine, DNA, is not expected to significantly contribute to the dissemination of genetic material encoding antibiotic resistance.


Plasmids containing the vaccine plasmid's type of origin of replication can only replicate in a limited range of bacterial hosts, which include E. coli and other related members of the Enterobacteriaceae family, and possibly members of the Legionellaceae family (Kües and Stahl, 1989). Although the tyrosinase gene present on the vaccine plasmid can be expressed in canine cells, the plasmid itself cannot replicate autonomously within a eukaryotic cell.


Following intramuscular administration of a plasmid DNA vaccine into an animal, some of the plasmid is taken up by myocytes surrounding the injection site, and possibly by some resident immune cells. Much of the remaining DNA is localized in the extracellular space, where it is subject to degradation by nuclease enzymes. Soon after inoculation, some plasmid DNA can be detected in the blood, although it is unclear how much of this DNA is intact plasmid. Nucleases are also present within blood and likely contribute to plasmid DNA degradation prior to clearance. Several minutes later, small quantities of plasmid DNA can be detected in the liver, spleen, draining lymph nodes, kidney, lungs, distant muscles, gonads and brain, presumably as a result of circulation within the bloodstream, and possibly via lymph and/or immune cells. Distribution to these vascularized organs is transient, and the only site where the intramuscularly injected plasmid appears to persist is in the muscle near the site of administration. Scavenger cells associated with the liver and kidney appear capable of clearing plasmid DNA from the circulation, and small DNA fragments may be eliminated by glomerular filtration. Plasmid DNA seems to be excreted in the urine and, to a lesser extent, in the feces (Parker et al., 1999; Dupuis et al., 2000; Kawase et al., 2003; Zang et al., 2005; Tonheim et al., 2008; Faurez et al., 2010). 041b061a72


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