• Title/Summary/Keyword: Cancer vaccines

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Prediction of Promiscuous Epitopes in the E6 Protein of Three High Risk Human Papilloma Viruses: A Computational Approach

  • Nirmala, Subramanian;Sudandiradoss, Chinnappan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4167-4175
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    • 2013
  • A najor current challenge and constraint in cervical cancer research is the development of vaccines against human papilloma virus (HPV) epitopes. Although many studies are done on epitope identification on HPVs, no computational work has been carried out for high risk forms which are considered to cause cervical cancer. Of all the high risk HPVs, HPV 16, HPV 18 and HPV 45 are responsible for 94% of cervical cancers in women worldwide. In this work, we computationally predicted the promiscuous epitopes among the E6 proteins of high risk HPVs. We identified the conserved residues, HLA class I, HLA class II and B-cell epitopes along with their corresponding secondary structure conformations. We used extremely precise bioinformatics tools like ClustalW2, MAPPP, NetMHC, Epi,Jen, EpiTop 1.0, ABCpred, BCpred and PSIPred for achieving this task. Our study identified specific regions 'FAFR(K)DL' followed by 'KLPD(Q)LCTEL' fragments which proved to be promiscuous epitopes present in both human leukocyte antigen (HLA) class I, class II molecules and B cells as well. These fragments also follow every suitable character to be considered as promiscuous epitopes with supporting evidences of previously reported experimental results. Thus, we conclude that these regions should be considered as the important for design of specific therapeutic vaccines for cervical cancer.

Clinical Benefit of Vaccinating Male Against HPV-related Disease (인유두종바이러스 관련 질환의 예방을 위한 남성 대상 백신의 임상적 유용성)

  • Lee, Sei Young
    • Korean Journal of Head & Neck Oncology
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    • v.38 no.1
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    • pp.11-16
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    • 2022
  • HHPV (Human Papillomavirus) is a DNA virus that can cause benign lesions, genitourinary cancer, and oropharyngeal cancer by penetrating the mucous membrane and skin. It is widely known to be transmitted mainly through sexual contact. As with many viral infections, vaccines have been developed to prevent infection with HPV. Currently, in many countries, HPV vaccines are mainly used for national immunization for women to prevent diseases that traditionally occur frequently in women, especially cervical cancer. However, since the vaccination rate is relatively low, many countries are struggling with ways to increase the vaccination rate. Meanwhile, the incidence of oropharyngeal cancer caused by HPV in men has been increasing recently. In the United States, the annual number of oropharyngeal cancers in men already exceeds the number of cervical cancers in women, so HPV infection in men has emerged as a major problem. Accordingly, interest in HPV vaccination in men has also increased, and studies on the effectiveness and necessity of vaccination of both women and men compared to women alone are being actively conducted. In this paper, the evidence of HPV vaccination for men will be reviewed through previous studies, and its validity and cost-effectiveness will be analyzed to bolster the clinical usefulness of HPV vaccination for men.

Evaluation of immunogenicity of the 2008-2009 seasonal influenza vaccines by microneutralization test

  • Kim, Seung Youn;Kim, Yun Kyung;Eun, Byung Wook;Kim, Nam Hee;Kang, Eun Kyeong;Lee, Byong Sop;Lim, Jung Sub;Lee, Jun Ah;Kim, Dong Ho
    • Clinical and Experimental Pediatrics
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    • v.55 no.12
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    • pp.474-480
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    • 2012
  • Purpose: For evaluating the immunogenicity of an influenza vaccine, the microneutralization (MN) test has a higher sensitivity and specificity as compared to the hemagglutination inhibition (HI) test. However, the MN test is more time consuming and is difficult to standardize. We performed the MN test to determine its usefulness as an alternative or complementary test to the HI test for evaluating the immunogenicity of influenza vaccines. Methods: We compared the MN test with the HI test using 50 paired samples taken from a previous clinical study (2008-2009) in Korean children under 18 years of age. Results: The linear correlation coefficients of the 2 tests for H3N2, H1N1, and influenza B were 0.69, 0.70, and 0.66, respectively. We identified a high index of coincidence between the 2 tests. For an influenza vaccine, the postvaccination seroprotection rates and seroconversion rates determined by the MN test were 78.0% and 96.0%, 90% and 42.0%, and 42.0% and 48.0% for H3N2, H1N1, and influenza B, respectively. Geometric mean titer fold increases of H3N2, H1N1, and influenza B were 2.89, 5.04, and 4.29, respectively, and were 2.5-fold higher. We obtained good results in the evaluation of the immunogenicity of the 2008-2009 seasonal influenza vaccines. Conclusion: We found that the MN test was as effective as the HI test. Therefore, we suggest that the MN test can be used as an alternative or complementary test to the HI test for evaluating the immunogenicity of influenza vaccines.

Cytotoxic T Lymphocytes Elicited by Dendritic Cell-Targeted Delivery of Human Papillomavirus Type-16 E6/E7 Fusion Gene Exert Lethal Effects on CaSki Cells

  • Wu, Xiang-Mei;Liu, Xing;Jiao, Qing-Fang;Fu, Shao-Yue;Bu, You-Quan;Song, Fang-Zhou;Yi, Fa-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2447-2451
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    • 2014
  • Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

The Reverse Proteomics for Identification of Tumor Antigens

  • Lee, Sang-Yull;Jeoung, Doo-Il
    • Journal of Microbiology and Biotechnology
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    • v.17 no.6
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    • pp.879-890
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    • 2007
  • The identification of tumor antigens is essential for the development of anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX (serological analysis of recombinant cDNA expression libraries) has been used to identify such tumor antigens by screening sera of patients with cDNA expression libraries. SEREX-defined antigens provide markers for the diagnosis of cancers. Potential diagnostic values of these SEREX-defined antigens have been evaluated. SEREX is also a powerful method for the development of anticancer therapeutics. The development of anticancer vaccines requires that tumor antigens can elicit antigen-specific antibodies or T lymphocytes. More than 2,000 antigens have been discovered by SEFEX. Peptides derived from some of these antigens have been evaluated in clinical trials. This review provides information on the application of SEREX for identification of tumor-associated antigens (TAA) for the development of cancer diagnostics and anticancer therapeutics.

Tumor Therapy Applying Membrane-bound Form of Cytokines

  • Kim, Young-Sang
    • IMMUNE NETWORK
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    • v.9 no.5
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    • pp.158-168
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    • 2009
  • Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

B Cells Transduced with HPV16 E6/E7-expressing Adenoviral Vector Can Efficiently Induce CTL-dependent Anti-Tumor Immunity

  • Kim, Yun-Sun;Ko, Hyun-Jeong;Kim, Yeon-Jeong;Han, Seung-Hee;Lee, Jung-Mi;Chang, Woo-Sung;Jin, Hyun-Tak;Sung, Young-Chul;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.7 no.3
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    • pp.109-116
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    • 2007
  • Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines

  • Manijeh, Mahdavi;Mehrnaz, Keyhanfar;Violaine, Moreau;Hassan, Mohabatkar;Abbas, Jafarian;Mohammad, Rabbani
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5973-5981
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    • 2013
  • At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

Global Controversies and Advances in Skin Cancer

  • Baldwin, Louise;Dunn, Jeff
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2155-2157
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    • 2013
  • Advances and controversies of skin cancer prevention in the Asian-Pacific region are to be examined in the world's first Global Controversies and Advances in Skin Cancer Conference to be held in Brisbane, Australia this November. APOCP Members are cordially invited to register early for the opportunity to contribute to the debate on a cancer which continues to be a prominent issue in the Asia Pacific and indeed worldwide. We need answers to the questions of why a cancer that is so preventable and easily detectable is still shrouded in controversy. Primary focuses will be on issues like viral involvement, vaccines and novel clinical approaches.