The development of a vaccine for tooth decay has been under investigation for more than 30 years. Cea plasmid as therapeutic dna vaccination against colorectal. V932 ad encodes human cea fused to ltb and the truncated version of human her2 tumor antigen her2ecdtm. In this study, cea dna vaccines plus anti41bb abs treatment was found to increase agspecific ctl activity and antitumor protective responses to mc32 cells. Dna vaccine for cancer immunotherapy benjamin yang1, jessica jeang1. Limited information is available regarding the ability of patients to mount an antibody response to this selfantigen following vaccination.
Human colon cancers express carcinoembryonic antigen cea. Several features of recombinant adenoassociated virus raav are attractive for. Dna immunization targeting carcinoembryonic antigen in colorectal. Therapeutic dna cancer vaccines are now considered a very promising strategy to activate the immune system against cancer. In 1972, a caries vaccine was said to be in animal testing in england, and that it would have begun human testing soon. V930 dna plasmids a and v932 adenoviral vector b encoding for her2neu and cea. In summary, systemic delivery of anti41bb abs slightly increased cea dna vaccinemediated agspecific ctl activity as well as antitumor responses to mc32 cells. In the past, several clinical trials using plasmid dna vaccines demonstrated a good safety profile and the activation of a broad and specific immune. Unlike traditional vaccines, dna vaccines stimulate both arms of the immune system offering long lasting immunity. Jci a novel transgenic mouse model for immunological. Yeastcea gi6207 is a therapeutic cancer vaccine genetically modified to express recombinant cea protein, using heatkilled yeast saccharomyces cerevisiae as a vector. Dna vaccine prepared using recombinant flagellin protein derived from salmonella as mucosal adjuvant for anticaries dna vaccine. Because the construction and mass production of dna vaccines are far easier than those of other conventional vaccine types live attenuated or killed vaccines, and subunit vaccines, as well as their advantages in biostability and biosafety, dna vaccines are thought of as a secondgeneration vaccine.
C4, and its expression was validated in hek293 cell line and in mice by electroporation in. We have also initiated programs to develop a multiantigen vaccine to treat chronic hepatitis b hbv infections, a vaccine to treat human papilloma virus hpvinduced cancers and a vaccine against tumor associated antigen muc1 that is associated with metastic progression of many cancer types including breast, ovarian, gastric, liver, pancreas. The recent developments in immunooncology have opened an unprecedented avenue for the emergence of vaccine strategies. Development of various vaccines for prostate cancer pca is becoming an active research area.
While various immunebased strategies can elicit antitumour responses, dna vaccines present increased efficacy, inducing both humoural and cellular immunity. Our approach has been to develop dna vaccines to stimulate antitumor immunity. Cancer vaccines targeting carcinoembryonic antigen. Carcinoembryonic antigen cea, an oncofetal protein with a relative molecular mass of 180,000, is considered to be an effective target for a dna vaccine because it is overexpressed by most colorectal, gastric, and pancreatic carcinomas, by 50% of breast cancers, and by 70% of nonsmall cell lung carcinomas. When the dna vaccine is administered to a patient, the machinery in their cells makes a viral or bacterial protein which their immune system. We studied this dna covaccination method in nonobese diabetic nod mice with autoimmune diabetes. Strategies for cancer therapy using carcinoembryonic antigen. Targeting carcinoembryonic antigen with dna vaccination. Both of these accomplishments represent examples of naked rna vaccines, meaning the mrna is. Dna vaccination for prostate cancer, from preclinical to.
Early clinical trials of dna vaccines against infectious patho gens have. Dna coding for the her2 and cea peptides v930 plus v932 i completed her2 andor cea expressing cancers nct00647114 merck. The v930 dnaep vaccine, in the initial phase 1 trial where dna vaccine alone was given study 1, was welltolerated, at both 0. The cancer vaccine 105ad7 is a human antiid mab that mimics the cd55 taa on crc cells. A loss of antitumor therapeutic activity of cea dna. Preventive dna vaccination against ceaexpressing tumors. Asp4070 astellas pharma us japanese red cedar allergy phase i immunotherapeutic plasmidbased northbrook, il. A novel dna vaccine design improves chances of inducing. Phase i trial of a recombinant yeastcea vaccine gi6207. Thus, cea has been considered as a potential vaccine target for immune therapy against colon cancer. C4 hybridoma cell line, which gave rise to antibodies able to recognize cea when c57bl6. The clinical trials on this list are studying adenoviral vector ad5cea6d vaccine. Tcell tolerance against tumor selfantigens, such as human.
A dnamodified live vaccine primeboost strategy broadens. Responses of mice immunized with a dna vaccine encoding carcinoembryonic antigen cea article in vaccine 2421. Both of them used the her2 cea dna vaccine v930 and showed the instauration of both humoral and cellular immune responses with no detectable immune response against the vaccine itself. Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective antitumor response. Clinical trials are research studies that involve people. Mechanisms and aspects of relevance for biosafety anne ingeborg myhr1 and roy a. Cea plasmid as therapeutic dna vaccination against. Clinical trials using adenoviral vector ad5cea6d vaccine. Characterization of antigenspecific immune responses induced by. Recombinant vaccinia viruses encoding fulllength or internally deleted. Ncis basic information about clinical trials explains the types and phases of trials and how they are carried.
Effective use of such vaccines is expected to benefit from proper. In the past, several clinical trials using plasmid dna vaccines demonstrated a. Carcinoembryonic antigen cea is a cancer vaccines target. Therapeutic vaccines for the stimulation of the immune system against tumor antigens and subsequent elimination of tumor cells have been. Carcinoembryonic antigen cea is a wellcharacterized oncofetal glycoprotein whose overexpression by human adenocarcinomas has been a target for cancer immunotherapy. Dna vaccines, electroporation and their applications in. Protective immunity against human carcinoembryonic antigen. Vaccination with dnacea induced much lower titers of anticea igg, which. Immunization with xenogeneic dna is an attractive approach to treat cancer since it generates t cell and antibody responses. Dna vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered dna to produce an immunological response. Ep101 epithany breast phase i multiantigen vaccine.
Several of these observations are being tested in clinical trials. A novel dna vaccine design improves chances of inducing antitumor immunity study results were published in the journal molecular therapy. The direct injection of genetic material into a living host causes a small amount of its cells to produce the introduced gene. Inhibition and promotion of tumor growth with adeno. In study 1, 71% of patients experienced a clinical noninjection site grade 1 or 2 ae, with fatigue 21% being the most common. Dna vaccines thus offer opportunities to incorporate genes encoding. Pca vaccines are perceived to have less toxicity compared with the available cytotoxic agents. Successful cancer vaccine therapy for carcinoembryonic. A novel transgenic mouse model for immunological evaluation of. Il12 plasmidenhanced dna vaccination against carcinoembryonic antigen cea studied in immunegene knockout mice article pdf available in gene therapy 718.
Introduction dna vaccine is dna sequence used as a vaccine. Carcinoembryonic antigen cea is expressed during embryonic life and in low level during adult life. The plasmid dna vaccine above carries the genetic code for a piece of pathogen or tumor antigen. Coinjection of a b71wa membranebound form plasmid blocked induction of anticea immunity, whereas a b71 plasmid was stimulatory. Psa is a serum marker that is widely used in the detection and monitoring of prostate cancer. Previously, we developed a dna vaccine using scfv6. Consequently, the cea is recognized by the immune system as a selfantigen and thus ceaexpressing tumors are tolerated. A caries vaccine is a vaccine to prevent and protect against tooth decay. All balbc mice boosted with rcea had strong anticea igg antibody response, while the responses in the c57bl6 mice were variable. This includes using antibodies directed against cea. August 2007,dna vaccination against sclerosis was reported as being effective. A lack of relevant animal models has hampered preclinical screening and critical evaluation of the efficacy of human vaccines in vivo.
The carcinoembryonic antigen cea is the main tumorassociated antigen of colorectal cancers. Successful cancer vaccine therapy for carcinoembryonic antigen cea. Mice immunized with dna and boosted with rcea had significantly higher levels of anticea igg antibodies than mice immunized with dna only fig. When the dna vaccine is administered to a patient, the machinery in their cells makes a viral or bacterial protein which their immune system recognises as being foreign to the body. Dna vaccination is a technique for protecting against disease by injection with genetically engineered plasmid containing the dna sequence encoding the antigens against which an immune response is sought so cells directly produce an antibody, producing a protective immunological response.
As cea and her2 are expressed by many solid tumors, patients with different types of cancer were recruited. In this study, we developed cea as a therapeutic dna vaccine. Responses of mice immunized with a dna vaccine encoding. C4 as a dna vaccine to prevent the growth of a tumor expressing cea in cea expressing transgenic mice cea2682. This antiid mab was produced by fusion of a mousehuman heteromyeloma cell line with lymphocytes from a patient previously injected with mouse mab 791t36 for tumor immunoscintigraphy austin et al. A dna vaccine uses a gene from a virus or bacteria to stimulate the immune system. Introduction dna vaccines represent a new approach to protect.
Dna immunization targeting carcinoembryonic antigen in. Strategies to enhance immunogenicity of dna vaccines against. Read a loss of antitumor therapeutic activity of cea dna vaccines is associated with the lack of tumor cells antigen presentation to agspecific ctls in a colon cancer model, cancer letters on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. There are many potential problems and unanswered questions concerning the use of dna vaccines. Phase 1 studies of the safety and immunogenicity of. We found that a loss of tumor cell sensitivity to ceaspecific ctlmediated killing might be associated with the lack of antitumor therapeutic activity of cea dna vaccines. Pdf dna vaccine for cancer immunotherapy researchgate. An immune response against cea atleast one time point was noted in. Novel dna vaccine design improves chances of inducing anti.
Previously, we constructed a single chain variable fragment using the 6. Il12 plasmidenhanced dna vaccination against carcinoembryonic. Protective immunity against human carcinoembryonic antigen cea induced by an oral dna vaccine in ceatransgenic mice 1 rong xiang, 2 steve silletti, 2 holger n. Two phase i studies show some results of therapeutic cancer dna vaccination nct00250419 and nct00647114. Research open access phase 1 studies of the safety and. Both of them used the her2cea dna vaccine v930 and showed the. Characterization of a messenger rna polynucleotide vaccine. Dna vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Cancer immunotherapy approaches, designed to harness the bodys natural immune defenses to target and kill cancer cells, are showing great promise for cancer treatment and prevention. Pdf dna vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Protective immunity against human carcinoembryonic. The main objective of this study was to evaluate scfv6. To overcome the weak immunogenicity of tumorassociated. In preclinical studies, yeastcea induced a strong immune response to cea and antitumor responses.
Figure 1 v930 dna plasmids a and v932 adenoviral vector b encoding for her2neu and cea. Safety and immunogenicity of a dna vaccine encoding. Scientists at the wistar institute and inovio pharmaceuticals, inc. Dnabased cancer vaccines designed to overcome peripheral. Novel dna vaccine design improves chances of inducing antitumor immunity based on a modified human antigen, this strategy could pave the way. The plasmid vector is taken up into cells and transcribed in the nucleus 1. The antituberculosis vaccine, bcg vaccine, is an example that is being tested to determine if it has a protective effect against covid. Human autoantibodies to carcinoembryonic antigen cea.
The antinucleoprotein antibody response induced by the dnamlv. Immunoinhibitory dna vaccine protects against autoimmune. Protective immunity against human carcinoembryonic antigen cea induced by an oral dna vaccine in cea transgenic mice article pdf available in clinical cancer research 73 suppl. Carcinoembryonic antigen cea, an oncofetal protein with a relative molecular mass of 180,000, is considered to be an effective target for a dna vaccine because it is overexpressed by most colorectal, gastric, and pancreatic carcinomas 6, by 50% of breast cancers, and by 70% of. Our tumorrelated ceadna vaccine constructs carrying immunomodulatory tet genes were further modified for expression at different cellular sites 23,24. The antidouble stranded dna antidsdna test is used to help diagnose lupus systemic lupus erythematosus, sle in a person who has a positive result on a test for antinuclear antibody ana and has clinical signs and symptoms that suggest lupus typically, an ana test is the first test performed to evaluate an individual for an autoimmune disorder.
70 1111 298 1181 1508 689 1346 35 1148 604 918 1435 998 1013 24 109 511 544 651 199 830 1407 34 203 288 365 300 1079 1545 877 1344 1646 228 1610 583 612 82 346 581 860 648 108 1415 931 85 1278 291 937 131