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11.
Carbohydrate vaccines that induce antibodies against cancer. 2. Previous experience and future plans
Philip O. Livingston Govindaswami Ragupathi 《Cancer immunology, immunotherapy : CII》1997,45(1):10-19
In conclusion The primary function of antibodies is the elimination of circulating viral or bacterial pathogens from the blood-stream, lymphatics
and interstitial spaces, and so, once induced, antibodies should be ideally suited for eliminating tumor cells and micrometastases
from these spaces as well. Natural or tumor-induced and vaccine-induced antibodies against human cancer-associated antigens
have been correlated with an improved clinical outcome. In the mouse, passive administration of monoclonal antibodies against
cell-surface antigens 1–4 days after tumor challenge, and active induction of antibodies with vaccines, has resulted in prolonged
survival or complete protection from tumor growth. This is a setting similar to the adjuvant setting in humans. Carbohydrates
are the most abundant antigens at the cell surface of cancer cells, where they play important roles in cell-cell interactions,
proliferation and the metastatic process. They have been shown to be excellent targets for immune attack by antibodies against
human cancers, especially in the adjuvant setting. Vaccines containing these carbohydrate antigens covalently attached to
immunogenic carrier proteins, such as KLH, plus potent immunological adjuvants, such as QS-21, effectively induce antibodies
against these antigens in patients, which can result in complement-mediated lysis of antigen-positive tumor cells. Phase III
trials with KLH conjugate vaccines have been initiated in the adjuvant setting against two carbohydrate antigens, the ganglioside
GM2 and the blood-group-related antigen sTn. As the immunogenicity of additional vaccines is confirmed in small pilot trials,
trials with polyvalent vaccines against two to five different antigens tailored for particular cancer types are planned. 相似文献
12.
Antioxidant defense responses: physiological plasticity in higher plants under abiotic constraints 总被引:4,自引:0,他引:4
Cheruth Abdul Jaleel Ksouri Riadh Ragupathi Gopi Paramasivam Manivannan Jallali Inès Hameed Jasim Al-Juburi Zhao Chang-Xing Shao Hong-Bo Rajaram Panneerselvam 《Acta Physiologiae Plantarum》2009,31(3):427-436
Environmental stresses (salinity, drought, heat/cold, light and other hostile conditions) may trigger in plants oxidative
stress, generating the formation of reactive oxygen species (ROS). These species are partially reduced or activated derivatives
of oxygen, comprising both free radical and non-radical (H2O2) forms, leading to cellular damage, metabolic disorders and senescence processes. In order to overcome oxidative stress,
plants have developed two main antioxidants defense mechanisms that can be classified as non-enzymatic and enzymatic systems.
The first class (non-enzymatic) consists of small molecules such as vitamin (A, C and E), glutathione, carotenoids and phenolics
that can react directly with the ROS by scavenging them. Second class is represented by enzymes among them superoxide dismutase,
peroxidase and catalase which have the capacity to eliminate superoxide and hydrogen peroxide. In this review, we have tried
to explore the related works, which have revealed the changes in the basic antioxidant metabolism of plants under various
abiotic constraints. 相似文献
13.
Ragupathi G Howard L Cappello S Koganty RR Qiu D Longenecker BM Reddish MA Lloyd KO Livingston PO 《Cancer immunology, immunotherapy : CII》1999,48(1):1-8
Sialyl-Tn (STn) is an O-serine- or O-threonine-linked disaccharide [NeuAcα(2→6)GalNAcα- O-Ser/Thr) expressed on mucins of most types of adenocarcinoma as single STn or clustered STn [STn (c)] epitopes. Though STn
is expressed on some normal tissues it is relatively tumor-specific, especially in the clustered conformation. Clinical trials
with STn-keyhole limpet hemocyanin (KLH) conjugate vaccines, prepared using reductive amination with a two-carbon linker group,
have resulted in high titers against STn but lower titers against natural forms of STn (ovine submaxillary mucin, or tumor
cells). To obtain antibodies of more appropriate specificity, we attempted to prepare STn(c)-KLH conjugates to establish their
immunogenicity in mice in preparation for clinical trials; however, conjugation efficiency was poor when the same two-carbon
linker was used, presumably because of steric hindrance. STn-KLH and STn(c)-KLH conjugates were prepared using the regular
two-carbon or the recently developed more efficient longer heterobifunctional 4-(4-maleimidomethyl)cyclohexane-1-carboxyl
hydrazide (MMCCH) linkers, and the resulting immunogenicities in mice were compared. The highest titers against STn were seen
with the STn-KLH conjugate with the two-carbon linker, and the highest titers against STn(c) were seen with STn(c)-KLH with
the MMCCH linker. Conjugation with MMCCH resulted in the highest conjugation efficiency (yield) and the highest titers against
ovine submaxillary mucin and STn-positive tumor cells, and is the method of choice for the preparation of STn(c) vaccine for
clinical trials.
Received: 30 October 1998 / Accepted: 18 December 1998 相似文献
14.
Ragupathi G Koide F Sathyan N Kagan E Spassova M Bornmann W Gregor P Reis CA Clausen H Danishefsky SJ Livingston PO 《Cancer immunology, immunotherapy : CII》2003,52(10):608-616
Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing this vaccine in the clinic, we tested the impact on antibody induction of administering the individual conjugates plus adjuvant compared with a mixture of the seven conjugates plus adjuvant, and of several variables thought to augment immunogenicity. These include approaches for decreasing suppressor cell activity or increasing helper T-lymphocyte activity (low dose cyclophosphamide or anti-CTLA-4 MAb), different saponin adjuvants at various doses (QS-21 and GPI-0100), and different methods of formulation (lyophilization and use of polysorbate 80). We find that: (1). Immunization with the heptavalent-KLH conjugate plus GPI-0100 vaccine induces antibodies against the seven antigens of comparable titer to those induced by the individual-KLH conjugate vaccines, high titers of antibodies against Tn (median ELISA titer IgM/IgG 320/10240), STn (640/5120), TF (320/10240), MUC1 (80/20480), and globo H (640/40); while lower titers of antibodies against Lewis(y)()(160/0) and only occasional antibodies against GM2 are induced. (2). These antibodies reacted with the purified synthetic antigens by ELISA, and with naturally expressed antigens on the cancer cell surface by FACS. (3). None of the approaches for further altering the suppressor cell/helper T-cell balance nor changes to the standard formulation by lyophilization or use of polysorbate 80 had any impact on antibody titers. (4). An optimal dose of saponin adjuvant, QS-21 (50 microg) or GPI-0100 (1000 microg), is required for optimal antibody titers. This heptavalent vaccine is sufficiently optimized for testing in the clinic. 相似文献
15.
Govindaswami Ragupathi R Rao Koganty Dongxu Qiu Kenneth O Lloyd Philip O Livingston 《Glycoconjugate journal》1998,15(3):217-221
STn (NeuAc26GalNAc-O-Ser/Thr) is a carbohydrate epitope overexpressed in various human carcinomas. Clinical trials are underway using synthetic STn or STn trimeric glycopeptides [STn, cluster; STn(c) conjugated with keyhole limpet hemocyanin (KLH) as active specific immunotherapy for these cancers. These vaccines have been prepared by conjugating a crotyl ethyl amide derivative of STn or STn(c) to KLH by direct reductive amination after ozonolysis. In the case of STn(c) the conjugation efficiency and the resulting epitope ratios were low. This may be due to steric hinderance of the short spacer arm. To overcome these difficulties, without resynthesis, the STn(c) glycopeptide was modified by attachment of an MMCCH (4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide) spacer arm to the aldehyde derivative, and then conjugated with thiolated KLH. This method gave a higher epitope ratio and yield than the direct method. The STn(c)-MMCCH-KLH conjugate induced high titer antibodies in mice against STn(c). This method may be generally applicable for large synthetic oligosaccharides. 相似文献
16.
Valery Kudryashov Govindaswami Ragupathi In Jong Kim Michael E Breimer Samuel J Danishefsky Philip O Livingston Kenneth O Lloyd 《Glycoconjugate journal》1998,15(3):243-249
Globo H (Fuc12Gal13GalNAc13Gal14Gal14Glc) is a carbohydrate structure that shows enhanced expression in many human carcinomas. From mice immunized with a globo H-KLH (keyhole limpet hemocyanin) synthetic conjugate an IgG3 monoclonal antibody (mAb VK-9) was derived that recognizes the globo H structure. Serological analysis showed that the minimal structure recognized by this mAb was the tetrasaccharide sequence Fuc12Gal13GalNAc13Gal. An isomeric structure with an internal GalNAc linkage was also recognized but less efficiently. mAb VK-9 did not react with many related structures, such as galactosylgloboside, globoside, H type 1, H type 2 blood group structures or fucosyl-gangliotetraosyl ceramide, but did react weakly with globo A ceramide. Not only did mAb VK-9 react with carbohydrate-protein conjugates but it could also recognize globo H-ceramide and human tumor cells expressing globo H. These results suggest that globo H-KLH could be explored as a vaccine in the treatment of carcinoma patients. 相似文献
17.
18.
Strengthening the laboratory diagnosis of pathogenic Corynebacterium species in the Vaccine era 下载免费PDF全文
S.K. Rajamani Sekar B. Veeraraghavan S. Anandan N.K. Devanga Ragupathi L. Sangal S. Joshi 《Letters in applied microbiology》2017,65(5):354-365
Over the last three decades, successful implementation of the diphtheria vaccination in the developed and developing countries has reduced the infections caused by the toxigenic strains of Corynebacterium diphtheriae, but a concomitant increase in the invasive infections due to the nontoxigenic strains was seen. In addition, the recent reports on the emergence of nontoxigenic toxin gene‐bearing strains, having the potential to revert back to toxigenic form poses a significant threat to human beings. Besides infections caused by C. diphtheriae, the emergence of the respiratory, cutaneous and invasive infections by related pathogenic Corynebacterium species like C. ulcerans and C. pseudotuberculosis, complicate the diagnosis and management of infection. These observations together with the widespread prevalence of diphtheria in the vaccine era, necessitates the strengthening of the epidemiological surveillance and laboratory diagnosis of the pathogen. This review provides the overview of the advantages and limitations of different molecular methods and the role of MALDI‐TOF in the laboratory diagnosis of Diphtheria. The contribution of next generation sequencing technology and different genotyping techniques in understanding the pathogenicity, transmission dynamics and epidemiology of the C. diphtheriae is discussed. 相似文献
19.
Dr K. Chitra N. Ragupathi K. Dhanalakshmi P. Mareeshwari N. Indra A. Kamalakannan 《Archives Of Phytopathology And Plant Protection》2013,46(1):50-56
Abstract The effect of Salicylic Acid (SA) in inducing resistance in groundnut plants against Alternaria alternata was investigated. Foliar application of SA at the concentration of 1 mM significantly reduced the leaf blight disease intensity and increased the pod yield under glasshouse conditions. Changes in the activities of phenylalanine ammonium lyase, chitinase β-1,3 glucanase and in phenolic content on groundnut after application of SA and inoculation with A. alternate were studied. In SA-treated leaves (plants) an increase in phenolic content was observed five days after challenge inoculation with A. alternata in groundnut plants pretreated with SA. There was a marked increase in chitinase and pathogen inoculation in SA-treated leaves. In chitinase, β-1,3 glucanase activities were observed in response to plants with an increase in SA treated leaves. Foliar applications of SA-induced in peroxidase and polyphenol oxidase activities were observed upon challenge inoculation with pathogen. 相似文献
20.
Combination of biocontrol agents that are compatible with each other is a strategic approach to control the plant disease and pest. The present study was designed to evaluate the protective effects of compatible endophytic bacterial strains (Bacillus subtilis; EPCO16 and EPC5) and rhizobacterial strain (Pseudomonas fluorescens; Pf1) against chilli wilt disease caused by Fusarium solani. Our results showed that B. subtilis (EPCO16 and EPC5) and P. fluorescens (Pf1) were compatible and effectively inhibited the growth of the F. solani. The application of endophytic and rhizobacterial strains, singly and in combination in green house and field conditions were found to be effective in controlling the chilli Fusarium wilt disease by inducing systemic resistance (ISR) as evidenced by enhanced activities of PO, PPO, PAL, β-1,3-glucanase, Chitinase and Phenolic involved in the synthesis of phytolaexins thereby promoting the growth of plants. However, combinations of EPCO16 + EPC5 + Pf1 bacterial strains were more effective than single agents. These findings suggest that synergistic interactions of biocontrol agents may be responsible for the management of chilli wilt disease caused by F. solani. 相似文献