Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine

Huang, Yujun; Fayad, Raja; Smock, Andrew; Ullrich, Amanda M.; Qiao, Liang

doi:10.1158/0008-5472.can-04-3669

Cited by 20 publications

(23 citation statements)

References 39 publications

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“…We have shown several lines of evidence that dendritic cell-based vaccination resulted in induction of CAP1-6D-specific CTL responses and combined vaccination strategy augmented CTL responses, which resulted in the in vivo tumor protection. Our results are in accordance with two recent publications suggesting the development of CTL response specific for CAP-1 in HLA-A2-Tg and CEA-A2Kb-Tg mice (48,49), and it has already been documented that CAP1-6D is more antigenic than CAP-1 (36).…”

Section: Discussionsupporting

confidence: 94%

Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 with a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen

et al. 2007

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Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8 + and CD4 + T cells. Immunization using dendritic cells loaded with tumor antigens constitute a powerful platform for stimulating cellular immunity. Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4 + T-helper responses in colon cancer patients as well as in mice transgenic for human CEA. Here, we have combined the anti-idiotype 3H1 with the CTL peptides of CEA to augment both T-helper and CTL responses in a clinically relevant mouse model, which is transgenic for both CEA and HLA-A2. We have evaluated the potential of two different HLA-A2-restricted epitopes of CEA pulsed into dendritic cells in a therapeutic setting. The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA 691 (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLS-GADLNL, agonist peptide for CAP-1)-pulsed dendritic cells. Mice immunized with peptide-pulsed dendritic cells along with 3H1-pulsed dendritic cells resulted in significant increase in survival compared with mice immunized with peptidepulsed dendritic cells alone (P < 0.02). IFN-; ELISPOT and 51 Cr-release assays showed that HLA-A2-restricted, CEAspecific CTL responses were augmented by combined dendritic cell vaccinations. The combined vaccination strategy resulted in increased antigen-specific proliferation of splenocytes and secretion of Th1 cytokines by CD4 + T cells that correlated with increased survival. These results suggest the potential use of this vaccination strategy for future clinical applications. [Cancer Res 2007;67(6):2881-92]

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Section: Discussionsupporting

confidence: 94%

Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 with a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen

et al. 2007

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“…Soluble folate-binding protein that is present in patients with ovarian cancer is an example of a glycosyl-phosphatidylinositol -linked tumor antigen shed into the serum (27). Carcinoembryonic antigen is another example of a glycosyl-phosphatidylinositol -anchored tumor antigen that is released into the serum of some patients with adenocarcinomas of the colon, rectum, stomach, pancreas, breast, and non -small cell lung cancer (28). Carcinoembryonic antigen is a useful marker for monitoring tumor recurrence especially in patients with colon cancer (29).…”

Section: Imaging Diagnosis Prognosismentioning

confidence: 99%

Detection and Quantitation of Serum Mesothelin, a Tumor Marker for Patients with Mesothelioma and Ovarian Cancer

Hassan¹,

Remaley²,

Sampson³

et al. 2006

Clinical Cancer Research

253

204

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Purpose: To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it. Experimental Design: We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma. Results: Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1and was undetectable by postoperative day 7. Conclusions: We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.Mesothelin is a cell surface protein present on normal mesothelial cells lining the body cavities. It is highly expressed in several cancers, including mesotheliomas, ovarian and pancreatic cancers, and some squamous cell carcinomas (1 -4). Human mesothelin is made as a 69 kDa polypeptide with a hydrophobic sequence at the carboxyl end that is removed and replaced by phosphatidylinositol. This glycosyl-phosphatidylinositol linkage anchors mesothelin to the cell membrane (1,5). After glycosylation at one or more of its four putative glycosylation sites, it is probably cleaved by the protease furin to yield a 32 kDa soluble protein called megakaryocyte potentiating factor (MPF) and a 40 kDa cell membrane bound protein called mesothelin. However, the proteolytic cleavage of mesothelin by furin has not been clearly shown for human tumors. MPF has been shown to potentiate megakaryocyte proliferation in mouse bone marrow cultures in the presence of interleukin-3 (6, 7). No data is available to show if MPF has megakaryocyte potentiating activity against human bone marrow precursors. The normal biological function of cell membrane -bound mesothelin is not known and mice with a knockout of the mesothelin gene have no obvious phenotype (8). A recent study presented evidence that mesothelin binds CA125 and may, therefore, play a role in the dissemination of ovarian cancer in...

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“…VLPs have been studied as oral vaccines against a variety of diseases [91][92][93][94]. They possess high affinity for intestinal mucosal surface receptors, which are easily recognized by expressed submucosal APC or intraepithelial lymphocytes.…”

Section: Virus-like Particlesmentioning

confidence: 99%

Oral delivery of nanoparticle-based vaccines

Marasini

Skwarczynski

Tóth

2014

Expert Review of Vaccines

134

100

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Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Therefore, vaccines delivered to the mucosal tissues can mimic natural infections and provide protection at the first site of infection. Thus, mucosal, especially, oral delivery is becoming the most preferred mode of vaccination. However, oral vaccines have to overcome several barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticle strategies are currently being explored to prepare stable oral vaccine formulations. This review briefly discusses several molecular mechanisms involved in intestinal immune cell activation and various aspects of oral nanoparticle-based vaccine design that should be considered for improved mucosal and systemic immune responses.

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Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine

Cited by 20 publications

References 39 publications

Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 with a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen

Therapy of Established Tumors in a Novel Murine Model Transgenic for Human Carcinoembryonic Antigen and HLA-A2 with a Combination of Anti-idiotype Vaccine and CTL Peptides of Carcinoembryonic Antigen

Detection and Quantitation of Serum Mesothelin, a Tumor Marker for Patients with Mesothelioma and Ovarian Cancer

Oral delivery of nanoparticle-based vaccines

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