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IDENTIFICATION OF PROSTATE CANCER ANTIGENS USING EXPRESSION CLONING TO DEVELOP VACCINES

Professor Robert C Rees, Dr Geng Li

School of Biomedical and Natural Sciences, Nottingham Trent University

The research undertaken by the Oncology Research Unit, School of Biomedical and Natural Sciences, Nottingham Trent University has benefited from the grant awarded by Prostate Research Campaign.   The £5000 from the Campaign has been used to purchase reagents essential for the experiments performed.   The following summarises the achievements made during the funding period.

Identification of tumour antigens from prostate cancer tissues

We have applied cloning techniques (SEREX) to identify tumour antigens from prostate cancer.   Three cDNA expression libraries were constructed from a well/moderately differentiated prostate adenocarcinoma, an undifferentiated prostate adenocarcinoma and an atypical adenomatous hyperplasia, respectively.   After screening half a million individual bacterial plaques of each cDNA library with autologous serum, 204 reactive clones were isolated.   They represent 103 different antigens.   Some of them have proved to be novel, while others correspond to previously known antigens including a metastasis associated antigen (MTA1), transcription factors, and mutated gene products.

We have developed array technologies which allow us to rapidly screen multiple expressed gene products from cDNA libraries against individual sera from patients with prostate cancer, BPH patients with other malignancies and normal control subjects.   We observed that the humoral immune response against some antigens in patients with prostate cancer was higher than that in patients with BPH and healthy controls.   The data infers that these antigens are able to elicit a humoral immune response in prostate cancer patients, and as such may be regarded as immunogenic proteins.

RT PCR has been used to evaluate mRNA expression pattern of the selected genes using a panel of RNA from normal tissues, BPH tissues, prostate cancer and other malignant tissues.

Clone Pr1 9 (a previously uncharacterised gene), Pr1 39 and MTA1 were over expressed in cancer tissues and normal testes but not in other normal tissues.

Related research using SEREX

The SEREX technique has been used by other collaborator to identify antigens associated with other cancers.   We have identified stomach cancer associated antigens and colon cancer associated antigens in collaboration with Dr Aija Line (Biomedical Research and Study Centre, University of Latvia), who has worked in the school on three occasions to conduct research with us.   Six over expressed in cancer tissues were identified.

Research summary dated 29 July 2005
Project 1998/01