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Biomedical subjects

A Fiander

Publications and source records attributed to A Fiander.

At least 19 recordsLinked to original sources
PubMed2003

Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R).

Human papilloma virus (HPV) found in 99.7% of cervical cancers represents an attractive immunotherapeutic target for novel adjuvant dendritic cell (DC) immunotherapy. DC primed with HPV antigens have been shown to be capable of inducing CTL responses powerful enough to eradicate established murine tumours expressing HPV16 antigen. The use of tumour lysate has been found to be an effective means of priming DC with tumour associated antigens in animal models and in clinical trials leading to significant anti-tumour responses. Autologous DC primed with sonicated HPV expressing tumour lysate have been shown to be capable of inducing HPV specific classes I and II T-cell immunity in a pilot clinical study.Synthetic double stranded polyribonucleotides are effective in vitro activation/maturation agents capable of inducing a stable mature DC phenotype producing high levels of IL12. However, the prototype polymer poly [I]:poly [G] has proved to be clinically toxic. Preliminary in vitro data have demonstrated that a novel clinically non-toxic analogue polymer poly [I]:poly [C(12)U] (Ampligen R) can effectively induce in vitro maturation of human monocyte derived DC with sustained bioactive IL12 production. Human monocyte derived DC primed with tumour lysate and matured with synthetic dsRNA may therefore offer an effective way of optimising Th1 specific anti-cancer T-cell responses in cancer patients. This strategy is currently being tested in a clinical trial in patients with cervical cancer.

Clinical Trials as Topic↗
PubMed2002

Follow-up after negative large loop excision of the transformation zone (LLETZ) of the cervix.

We performed a retrospective analysis of 204 patients who underwent large loop excision of the transformation zone (LLETZ) to determine whether women who have a negative LLETZ (no cervical intra-epithelial neoplasia (CIN) present) are at a lower risk of developing further abnormal cytology or CIN than women whose LLETZ is positive (CIN present). Overall 69 of the LLETZ samples were negative (34%) and 135 were positive (66%). The mean duration of negative cytology during follow up was 25.4 months (negative LLETZ) and 21.2 months (positive LLETZ) (P=0.03). In the negative LLETZ group, cytology did not miss any cases of persistent CIN at the 6-month follow-up visit and 39 repeat punch biopsies were all negative. There were 3/69 cases (4.3%) in the negative LLETZ group and 13/135 (9.6%) in the positive LLETZ group of persistent disease (CIN diagnosed at or as a result of the 6-month follow-up). Following a negative 6-month review, one woman developed an abnormal smear in the negative LLETZ group (1/66=1.5%) compared with 10 women (10/122=8.1%) in the positive LLETZ group. Recurrent CIN (CIN subsequently diagnosed following a negative 6-month review) was seen in 0/69 cases (0%) in the negative LLETZ group and 4/135 (3.2%) in the positive LLETZ group. We conclude that women who undergo a negative LLETZ may represent a low-risk group for developing further cytological and histological abnormalities.

Adult↗
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

Immunology of human papillomavirus infection in lower genital tract neoplasia.

Despite its being a relatively common virus, the study of human papillomavirus infection has lagged behind that of other viruses. Human papillomaviruses do not provoke strong systemic antibody or T-cell responses. Furthermore, the majority of those infected do not display clinical symptoms and are able to clear the virus by unknown mechanisms. In the last decade, however, research into human papillomavirus immunology has blossomed, for two main reasons. First, there is strong circumstantial evidence that the immune system can control papillomavirus infection, since the prevalence of human papillomavirus-associated neoplasia is increased in immunocompromised individuals. Second, the strong association between human papillomavirus infection and cervical cancer has led to attempts to develop prophylactic or therapeutic vaccines. In this chapter, our current knowledge of human papillomavirus immune responses will be reviewed, and how this relates to clinical practice will be discussed.

CD4-Positive T-Lymphocytes↗
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↗
PubMed1995

Evaluation of flexible senior registrar training in obstetrics and gynaecology.

OBJECTIVE: To evaluate part-time senior registrar training in obstetrics and gynaecology from the perspective of the trainees. DESIGN: Postal questionnaire. SUBJECTS: Past and present senior registrar trainees on the PM(79)3 scheme. RESULTS: Thirty-two questionnaires were returned (86% response rate) from 20 current trainees (100% response) and 12 (71% response) past trainees. Family commitments were the main reason for training part-time. Of these, 84% were satisfied with their training and most (81%) thought the quality as good or better than full time training. Personalised timetables were seen to be of particular benefit. Negative attitudes towards part-time training and discrimination in favour of full time trainees were seen as some of the biggest difficulties associated with part-time training. Other problems included administrative delays in organising part-time posts, time restriction, and the length of training. CONCLUSIONS: Part-time senior registrar training is effective in retaining trainees with domestic commitments within the speciality. It is regarded as being of high quality but with attendant problems, particularly those related to the negative attitudes of others. Recommendations for improvements have been made.

Attitude of Health Personnel↗