Immunologic responses to xenogeneic tyrosinase dna vaccine. Immunization with xenogeneic dna encoding tyrosinase family proteins has been shown to induce antibody, t cell, and antitumor responses in mice and a small cohort of dogs. This vaccine, based on a dna vector, was generally well tolerated in a study of 111 dogs. To further define the optimal vaccination strategy, we conducted a phase i study of in vivo electroporation ep of a murine tyr dna vaccine pingmutyr in malignant melanoma. We conducted a trial of mouse and human tyr dna vaccines in stage iiiiv melanoma patients. Researcher eyes vaccines to treat canine skin cancer. The xenogeneic cmmp7 induced immune responses can be evidenced by strong antibody response, elevated ifn. Xenogeneic definition of xenogeneic by merriamwebster. Vaccination with human tyrosinase dna induces antibody responses in dogs with advanced melanoma. A similar vaccine has been created for equine melanoma and is currently being studied at the university of. Rhcea cdna was codonusage optimized rhceaopt and delivered by sequential dna electrogenetransfer dna egt and adenoviral ad vector. Xenogeneic immunization using human tyrosine hydroxylase dna vaccine in established neuroblastoma has also resulted similar outcome in mouse model.
Her2neu dna immunization for patients with metastatic and high risk breast cancer. Such cells, tissues or organs are called xenografts or xenotransplants. Patients received three immunisations and subsequently patients who had received homologous vaccination. Although dna vaccines have induced immune responses to viral proteins, vaccinating against tissue specific selfproteins on cancer cells is clearly a more difficult problem. Among the first clinical trials was a vaccine encoding psa in patients with hormonerefractory prostate cancer led by pisa and colleagues.
One way to induce immunity against a tissue specific differentiation antigen on cancer cells is to vaccinate with xenogeneic antigen or dna that is homologous to the cancer antigen. Longterm survival of dogs with advanced malignant melanoma. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumorbearing mice. Preclinical mouse studies have shown that xenogeneic dna vaccination with genes encoding tyrosinase family members can induceantibody and cytotoxic tcell responses, resulting in tumor rejection. We have generated a xenogeneic vaccine against human carcinoembryonic antigen hceacam5 or commonly hcea using as immunogen rhesus cea rhcea.
Xenotransplantation xenosfrom the greek meaning foreign or strange, or heterologous transplant is the transplantation of living cells, tissues or organs from one species to another. Xenogeneic definition is derived from, originating in, or being a member of another species. Immunotherapy of tumors with xenogeneic endothelial cells. Importantly, these antibodies did not boost systemic immune responses and instead altered immune activation in the tumor. Ctla4 blockade in combination with xenogeneic dna vaccines enhances tcell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems. Safety of administering the canine melanoma dna vaccine. Objectiveto evaluate the safety and efficacy of a vaccine containing plasmid dna with an insert encoding human tyrosinase ie, hutyr vaccine as adjunctive treatment for oral malignant melanoma mm in dogs animals111 dogs 58 prospectively enrolled in a multicenter clinical trial and 53 historical controls with stage ii or iii oral mm modified world health organization staging scale. Definition of xenogeneic tyrosinase dna vaccine nci drug. Safety and immunogenicity of a melanoma dna vaccine delivered. Bergman pj1, campspalau ma, mcknight ja, leibman nf, craft dm, leung c, liao j, riviere i, sadelain m, hohenhaus ae, gregor p, houghton an, perales ma, wolchok jd. Impact for human medicineresponse to dna vaccination in dogs with oral mm may be useful in development of plasmid dna vaccination protocols for human patients with similar disease. Superior immunologic and therapeutic efficacy of a xenogeneic.
May 09, 2007 immunologic responses to xenogeneic tyrosinase dna vaccine administered by electroporation in patients with malignant melanoma. Xenogeneic silencing and its impact on bacterial genomes. Nevertheless, several strategies are available to enhance dna vaccineinduced immune responses in the patient. The use of fetal tissue in vaccine development is the practice of researching, developing, and producing vaccines through the use of cultured laboratorygrown human fetal cells. In this issue of molecular therapy, duperret et al. A complex dna vaccine construct that delivers several xenogeneic epitopes dramatically increased the ctl antitumor activity 46. Systematic evasion of the restrictionmodification barrier. Development of a xenogeneic dna vaccine program for canine malignant melanoma at the animal medical center. Il18 immunoadjuvanted xenogeneic canine mmp7 dna vaccine. Immunotherapy of tumors with xenogeneic endothelial cells as. Apr, 2015 we have generated a xenogeneic vaccine against human carcinoembryonic antigen hceacam5 or commonly hcea using as immunogen rhesus cea rhcea.
The hns heatstable nucleoid structuring protein affects both nucleoid compaction and global gene regulation. Thus, earlier studies showed that xenogeneic dna vaccines not only induce immune responses against the foreign protein but also generate autoreactive ctls that recognize the homologous host protein by crosspriming 12, 22. Strategies to enhance immunogenicity of dna vaccines against selfantigens have been investigated including encoding of xenogeneic versions of antigens, fusion. Safety and immunogenicity of tyrosinase dna vaccines in. Safety and efficacy of a xenogeneic dna vaccine encoding for. Immunogene therapy of tumors with vaccine based on. Request pdf il18 immunoadjuvanted xenogeneic canine mmp7 dna vaccine overcomes immune tolerance and supresses the growth of murine mammary tumor the development of the tumorigenesis and. Safety and immunogenicity of a potential checkpoint. Rhcea cdna was codonusage optimized rhceaopt and delivered by sequential dna electrogenetransfer dnaegt and adenoviral ad vector. Xenogeneic definition of xenogeneic by the free dictionary. The first clinical trail, initiated to monitor the safety and efficacy of a dna vaccine against hiv1 infection, demonstrated that dna plasmid vaccines were safe and were capable of inducing detectable immune cellular and antibody responses 4042. A phase i study to assess safety and immunogenicity the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The effects and mechanism of xenogeneic adipocyte vaccine for. Canine malignant melanoma cmm is a spontaneous, aggressive, and metastatic neoplasm.
A complex dna vaccine construct that delivers several xenogeneic epitopes dramatically increased the ctl antitumor activity. Most vaccines currently available were developed using cell strains cultured from two fetuses aborted for other. Enhancement of dna vaccine efficacy by targeting the xenogeneic human chorionic gonadotropin, survivin and vascular endothelial growth factor receptor 2 combined tumor antigen to the major histocompatibility complex class ii pathway. Dna vaccines have been proposed as potential solutions for poultry diseases since they are subunit vaccines with no risk of infection or reversion to virulence. Another strategy effectively break tolerance against selfantigens is. A xenogeneic human tyrosinase dna vaccine was developed for treatment of dogs with oral malignant melanoma oncept. Enhancement of dna vaccine efficacy by targeting the. Request pdf xenogeneic murine tyrosinase dna vaccine for malignant melanoma of the digit of dogs malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. From april 2000 to present, approximately 170 dogs with previously histologically confirmed spontaneous malignant melanoma were treated with xenogeneic dna vaccinations. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. These studies provided the rationale for a trial of xenogeneic dna vaccination in.
A similar vaccine has been created for equine melanoma and is currently being studied at the university of floridas college of veterinary medicine. Currently, a vaccine exists for canine melanoma that has shown good efficacy. To test this concept, we constructed a plasmid dna encoding xenopus vegf xvegfp. Hns appears to act primarily as a silencer of atrich genetic material acquired by horizontal gene transfer. Several of these observations are being tested in clinical trials. The efficacy of dna xenovaccines was also tested in dogs 47, leading to the approval of the first xenogeneic dna vaccine against human tyrosinase, oncept, for the treatment of oral malignant melanoma in dogs 43. Safety and efficacy of a xenogeneic dna vaccine encoding. The effects and mechanism of xenogeneic adipocyte vaccine for the prevention of obesity in rats qg lai, bq jiang, xh zhou, x xu, zn gao, and kf yuan journal of international medical research 2010 38. Oct 29, 2006 xenogeneic her2neu dna immunization for patients with metastatic and high risk breast cancer. We demonstrated that xenogeneic tert dna vaccine induced effective tumor antigenspecific immunity against murine breast cancer expressing tert both in prophylactic and therapeutic vaccine model.
The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. These studies provided the rationale for a trial of xenogeneic dna vaccination in cmm using the human. The vaccines themselves contain none of the original cells and only very slight traces of human dna. Dna vaccines encoding xenogeneic differentiation antigens, such as tyrosinase tyr, mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. Thus, xenogeneic dna vaccination could break tolerance against a self tumor differentiation antigen, inducing antibody, tcell and antitumor responses. Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. The first dnabased canine cancer vaccine, now fully. Conclusions and clinical relevanceresults support the safety and efficacy of the hutyr dna vaccine in dogs as adjunctive treatment for oral mm. At present, there are limited outcome data for dogs with omm treated with surgery and immunotherapy. Another strategy effectively break tolerance against selfantigens is the use of xenogeneic dna vaccines. Immunity to self antigens on cancer is constrained by toleranceignorance. Derived or obtained from an organism of a different species.
Xenogeneic immunization with human tyrosine hydroxylase dna. No studies have evaluated the safety or efficacy of this vaccine in cats. Their safety in terms of adverse reactions after injection has been demonstrated in animal models 38, 39 as well as in human clinical trials. Nov 24, 2006 using wholetumor cells transfected with xenogeneic mmp2 as an alternative dna vaccine, we found that an autoreactive immune response against the mmp2positive tumor cells may be provoked in a. Table 2 summarizes the clinical trials for prostate cancer using dna vaccines that have been conducted to date. Determine if a novel xenogeneic dna vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Recent advances in delivery of veterinary dna vaccines. T1 enhancement of dna vaccine efficacy by targeting the xenogeneic human chorionic gonadotropin, survivin and vascular endothelial growth factor receptor 2 combined tumor antigen to the major histocompatibility complex class ii pathway. Xenogeneic murine tyrosinase dna vaccine for malignant. Longterm survival of dogs with advanced malignant melanoma after dna vaccination with xenogeneic human tyrosinase. Development of a xenogeneic dna vaccine program for canine. Apr 16, 2004 preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective antitumor response. Pdf ctla4 blockade in combination with xenogeneic dna. Request pdf il18 immunoadjuvanted xenogeneic canine mmp7 dna vaccine overcomes immune tolerance and supresses the growth of murine mammary tumor.
Metastatic disease is a common sequela for which few effective treatment options exist. Immunization against defined tumor antigens using a xenogeneic dna vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and nonhodgkins lymphoma. When working in concert, these mechanisms may improve the efficacy of vaccines. In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. A murine xenogeneic dna vaccine for canine oral malignant melanoma was recently evaluated. As such, it is key in the regulation of most genes involved in virulence and in adaptation to new environmental niches. Jan 15, 2016 a xenogeneic dna vaccination has been licensed for use in dogs with locally controlled stage ii and iii oral malignant melanoma omm. The results of these trials demonstrate that xenogeneic dna vaccination in cmm. Immunity against breast cancer by tert dna vaccine primed. The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer theraphy. Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective antitumor response. Schematic diagram of bivalent xenogeneic dna vaccine construct and its mechanism of action.
Superior immunologic and therapeutic efficacy of a. Dna vaccines for prostate cancer europe pmc article. Xenogeneic definition of xenogeneic by medical dictionary. Studies show that xenogeneic tyrosinase dna vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. A plasmid dna vaccine, encoding an epitope of mouse tyrosinase, with potential antineoplastic activity. Xenogeneic immunization with human tyrosine hydroxylase. Xenogeneic her2neu dna immunization for patients with.
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