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A S Evans

Publications and source records attributed to A S Evans.

At least 19 recordsLinked to original sources
PubMed2001

Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6.

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with the development of cervical cancer. The E6 and E7 proteins of HPV are constitutively expressed in cervical carcinoma cells making them attractive targets for CTL-based immunotherapy. However, few studies have addressed whether cervical carcinomas can process and present HPV E6/E7-derived Ags for recognition by CTL. We generated HLA-A*0201-restricted CTL clones against HPV16 E6(29-38) that recognized HPV16 E6 Ags transfected into B lymphoblastoid cells. These CTL were unable to recognize HLA-A*0201(+) HPV16 E6(+) cervical carcinoma cell lines even when the level of endogenous HPV16 E6 in these cells was increased by transfection. This defect in presentation of HPV16 E6(29-38) correlated with low level expression of HLA class I, proteasome subunits low molecular mass protein 2 and 7, and the transporter proteins TAP1 and TAP2 in the cervical carcinoma cell lines. The expression of all of these proteins could be up-regulated by IFN-gamma, but this was insufficient for CTL recognition unless the level of HPV16 E6 Ag was also increased by transfection. CTL recognition of the HPV16 E6(29-38) epitope in 721.174 B cells was dependent on TAP expression but independent of immunoproteasome expression. Collectively, these findings suggest that presentation of the HPV16 E6(29-38) epitope in cervical carcinoma cell lines is limited both by the level of TAP expression and by the low level or availability of the source HPV E6 oncoprotein. These observations place constraints on the use of this, and potentially other, HPV-derived CTL epitopes for the immunotherapy of cervical cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer.

Cervical cancer is the second most common cause of cancer death in women worldwide. It is almost invariably associated with infection with human papilloma virus (HPV) particularly types 16 and 18. The ubiquitous expression of E6 and E7 oncogene products has been recognised as an attractive target for CTL-mediated immunotherapy. In-vivo expansion of an HPV oncogene product specific MHC class 1 restricted response has been demonstrated using intradermally administered live vaccinia virus HPV 16 and 18 E6/E7 gene construct (TA-HPV, Cantab Pharmaceuticals). Responses have been seen in 1/3 evaluable patients with advanced cervical cancer, and 3/12 CIN3 volunteers, and in 4/29 patients with early invasive cervical cancer (Rankin et al. Proceedings of 91st AACR Meeting, San Francisco, April 2000). In addition, the adoptive transfer of ex vivo HPV 16 or 18 positive autologous tumour lysate pulsed dendritic cells is currently being tested as an alternative means of expanding HPV specific CTL in advanced cervical cancer patients. So far an HLA-A*O201 restricted CD8 T cell response has been recorded in the single HLA-A*O201 patient whose tumour was shown to be HPV16 positive. It appears therefore feasible to induce HPV specific CTL responses in patients with cervical cancer using several vaccine strategies. However, further clinical trials are needed to determine the full anti-tumour potential of this vaccine based immunotherapy.

Adoptive Transfer↗
PubMed2001

Physiological variation among Populus fremontii populations: short- and long-term relationships between delta13C and water availability.

Different populations of widely distributed species can experience dramatically different climatic conditions that may influence physiological activity, specifically carbon assimilation and water use. Populus fremontii Wats. (Fremont cottonwood) populations are found near rivers of varying size along a precipitation gradient from New Mexico to northern California. Climatic differences among populations may lead to physiological differences because P. fremontii is sensitive to water availability. To assess physiological variation among populations, we collected foliage and wood samples from 13 populations that experience different precipitation and stream flow regimes and analyzed the samples for carbon isotope composition (delta13C). Wood delta13C served as a lifetime-averaged indicator of water-use efficiency (WUE), whereas foliage delta13C provided as an estimate of WUE during the growing season of collection. We found approximately 3.4 per thousand variation in delta13C among populations for both foliage (-31.1 to -27.9 per thousand) and wood (-28.3 to -24.7 per thousand). Wood delta13C was, on average, 2.8 per thousand more enriched than foliage. Some of the variation in wood delta13C can be explained by variation in elevation of the study sites. We constructed total precipitation and mean stream flow variables based on the length of the growing season at each study site and analyzed for a relationship between delta13C, precipitation and stream flow. A significant relationship between foliage delta13C and precipitation was found, but water availability did not explain a significant fraction of the variation in wood delta13C. The data suggest that water availability can account for some of the delta13C variation among populations but, given the large residual variances, other factors are important.

California↗
PubMed1997

Infiltration of cervical cancer tissue with human papillomavirus-specific cytotoxic T-lymphocytes.

CTLs specific for high-risk human papillomaviruses (HPVs) have recently been found in the peripheral blood of cervical cancer patients. Although cell-mediated immunity is thought to be important in the control of HPV infection, the functional relevance and site of activation of HPV-specific CTLs are unclear. We identified HLA-A*0201-restricted HPV-16 E7 peptide-specific CTLs in the peripheral blood (four of five patients), draining lymph nodes (three of four patients) and tumors (one of three patients) of cervical cancer patients. In four of four cancer patients, the frequency of CTLs specific for a recombinant vaccinia virus expressing HPV-16 and -18 E6/E7 gene products was found to be higher in tumors and lymph nodes compared with that of peripheral blood. HPV-specific CTLs were not identified in any of seven healthy controls, but primary responses could be generated by peptide-pulsed dendritic cells (four of four controls). In a non-HLA-A*0201 subject with invasive carcinoma, other HLA alleles also presented HPV antigens. This is the first demonstration that virus-specific CTLs infiltrate the virus-associated tumor, where they may play an important role in restricting disease progression.

Adult↗
PubMed1996

Human T-cell lymphotropic virus type I infection in Barbados: results of a 20-year follow-up study.

Forty-one human T-cell lymphotropic virus type I (HTLV-1)-seropositive individuals were identified among 1,012 subjects with stored serum samples from a health and seroepidemiological survey conducted in Barbados in 1972. These 41 subjects plus 79 HTLV-1 seronegative household members were targeted in a follow-up study 20 years later. Sixteen seropositive subjects and 22 seronegative subjects were interviewed, examined, and phlebotomized. There were no changes in HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19%) of the seropositive subjects had HTLV-1-associated disorders: two with dermatitis and one with "smoldering" adult T-cell leukemia. Neurologic and immunologic function was similar in HTLV-1-seropositive and HTLV-1-seronegative subjects. HTLV-1 antibodies persist over many years, and the risk for seroconversion of household contacts is low.

Adolescent↗
PubMed1996

A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection, especially with type 16 or 18, is associated with cervical cancer. Two HPV proteins, E6 and E7, are consistently expressed in tumour cells. The objectives of the study were to examine the clinical and environmental safety and immunogenicity in the first clinical trial of a live recombinant vaccinia virus expressing the E6 and E7 proteins of HPV 16 and 18 (TA-HPV). METHODS: The study was an open label phase I/II trial in eight patients with late stage cervical cancer. The patients were vaccinated with a single dose of TA-HPV and kept in strict isolation to monitor local and systemic side-effects, environmental spread, and anti-E6/E7 immune responses. FINDINGS: Vaccination resulted in no significant clinical side-effects and there was no environmental contamination by live TA-HPV. Each patient mounted an antivaccinia antibody response and three of the eight patients developed an HPV-specific antibody response that could be ascribed to the vaccination. HPV-specific cytotoxic T lymphocytes, the effector mechanism most likely to be of therapeutic benefit, were detected in one of three evaluable patients. INTERPRETATION: Further studies to investigate the use ot TA-HPV for immunotherapy of cervical cancer are warranted.

Adult↗
PubMed1996

Cytotoxic T cell immunity to human cytomegalovirus glycoprotein B.

Human cytomegalovirus (HCMV) is associated with significant morbidity and mortality following immunosuppression and in pregnancy. HCMV infection may be accompanied by acute disease but persists asymptomatically. Cytotoxic T lymphocytes (CTL) appear to be an important immune effector mechanism in maintaining the normal host-virus equilibrium. Glycoprotein B may be an important target for future subunit vaccines as it has been found to elicit both neutralising antibody and CTL responses. We therefore studied the ability of normal asymptomatic HCMV-seropositive individuals and women throughout pregnancy to determine the presence of HCMV and gB-specific CTL responses. CTL effector cells were induced by stimulation of peripheral blood mononuclear cells (PBMC) with AD169 HCMV-infected cells and gB-specific CTL were identified using chromium labeled, vac.gB-infected cells. In 7 HCMV-seropositive individuals, HCMV-specific CTL were identified. Three of the 7 individuals which lysed HCMV-infected cells lysed vac.gB-infected B cells. However, vac.gB-infected autologous fibroblasts, which only present MHC class I, were not killed. Using MHC class I single allele targets, no specific lytic response was observed, suggesting a MHC class II restricted CTL response. Flow cytometric analysis showed the gB-specific effector cell phenotype to be CD3+, CD4+, CD8-. In conclusion, a gB-specific CTL lytic response was identified in seropositive individuals which in most cases was MHC class II-restricted.

Adult↗
PubMed1994

Evaluation of Epstein-Barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease.

We assessed the relationship of Epstein-Barr virus (EBV) serology to the presence or absence of EBV genome in 39 cases of Hodgkin's disease (HD). Biopsies from patients included in 2 previous published studies, 1 involving patients from the United States (eastern Massachusetts) and 1 from Denmark, were evaluated for EBV (EBER-1) and latent membrane protein (LMP-1). The presence of EBV in Reed-Sternberg cells in the biopsies correlated with the histologic subtype of HD (mixed cellularity and lymphocyte depletion) but not with IgG antibody titers against the viral capsid antigen (VCA). These data suggest that, unlike Burkitt's lymphoma, the IgG antibody against VCA is not predictive of the presence or absence of EBV in Reed-Sternberg cells in HD. The predictive value of other antibodies should be evaluated.

Adult↗
PubMed1992

The past is prologue: use of serum banks in cancer research.

In this paper, we emphasize the uses of serum banks in cancer research. These include not only case/control studies but also prospective seroepidemiological studies in which the development of a serological marker, such as a viral antibody or viral antigen, can be correlated with the subsequent development of cancer in either an active surveillance program or the use of cancer registries or hospital records. Several different methods of application of the cohort technique are illustrated by studies of hepatitis B antigen and hepatocellular carcinoma and of Epstein-Barr virus in relation to African Burkitt's lymphoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Collections of sera done for one purpose can often be utilized for another purpose, if properly stored and documented. Two examples are tests for human T-cell leukemia virus, type 1, antibody from sera done for a health survey in Barbados approximately 8 years earlier and the use of data determined for a prospective study of the incidence of Epstein-Barr virus infection and infectious mononucleosis in West Point Cadets for psychological factors affecting the development of clinical illness among those infected. Archival materials, such as frozen tissues and paraffin sections, may also now be utilized for identifying genomes of potential oncogenic viruses by the polymerase chain reaction.

Blood Banks↗
PubMed1990

Viruses and cancer. Causal associations.

This review first considered some general problems in establishing causal links between a virus and a human cancer and offered some guidelines in the pursuit of this objective. Second, it reviewed the current causal associations for several candidate oncogenic viruses in relation to the tumors with which they are associated. These include Epstein-Barr virus in relation to Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and non-Hodgkin's lymphoma; hepatitis B and C viruses in relation to hepatocellular carcinoma; human T-cell leukemia/lymphoma virus type 1 and atypical leukemia/lymphoma; and human papilloma viruses in relation to cervical carcinoma. For some, the causal relationship is strong: hepatitis B virus with hepatocellular carcinoma, and human T-cell leukemia/lymphoma virus with adult T-cell leukemia/lymphoma. For one, the causal relationship is moderate: Epstein-Barr virus with African Burkitt's lymphoma. For others it is incomplete or inconclusive: Epstein-Barr virus with Hodgkin's disease and non-Hodgkin's lymphoma, and hepatitis C virus with hepatocellular carcinoma. Current techniques do not permit an answer for some: human papilloma virus with cervical carcinoma.

Animals↗
PubMed1989

A historical study of human T lymphotropic virus type I transmission in Barbados.

A 1972 historic sera collection from two health districts in Barbados, British West Indies, was evaluated for risk factors and epidemiologic patterns of HTLV-I (human T cell leukemia virus type I) during a time prior to the first report of its discovery in 1980. HTLV-I seroprevalence is 4.2% (43 of 1,012) and is consistent with current estimates in endemic areas in the Caribbean. Age-dependent rise (P less than .01) and higher seroprevalence rates for females (P less than .01) are indistinguishable from the pattern in contemporary Caribbean and Japanese populations. HTLV-I seropositivity was 4 times higher in women (P less than .003) and 2.6 times higher in men (P = .32) with treponemal antibodies, supporting a role for sexual transmission. Children who were positive in a household were more likely to have a seropositive mother than a seropositive father. This pattern is consistent with transmission of the virus from mother to child. Our results document that rates of infection and modes of transmission of HTLV-I are persistent.

Adolescent↗