Peter Johnson - Overview
The Cancer Research UK Wessex Medical Oncology Unit carries out basic,
translational and clinical research.
Immunology research addresses the processing of antigens in the MHC pathways,
the mechanisms of antigen presentation and the processes by which tolerance
is established and may be broken.
Molecular mechanisms of MHC Class-I restricted antigen processing and
presentation. We have identified the key molecules involved in loading
MHC Class I molecules with antigenic peptides for presentation to cytotoxic
T cells, and have begun to elucidate the mechanisms by which this occurs.
Tumour antigens. We have shown that cytotoxic T-cells can specifically
recognise post-translational modifications on peptide antigens and aim
to exploit this in the investigation of tumour-specific responses.
The regulation of T cell responses to tumours. We have established that
regulatory T cells determine the efficacy of anti-tumour responses in
a model system. We have also shown that fully capable dendritic cells
may present a self-epitope with altered peptide ligand features that can
unexpectedly induce anergy in a human autoreactive T cell clone. This
indicates that presentation of a self-epitope by immunologically competent
dendritic cells does not always mean "danger" and suggests a
mechanism involved in the fine balance between activation and tolerance
induction.
Apoptosis research is directed at understanding the control of cell survival
and programmed cell death by members of the Bcl-2 gene family.
BAG-1 We have been instrumental in understanding the mechanisms that
control BAG-1 expression and were the first to show that cells express
three differentially localised BAG-1 isoforms through alternate translation
of a single mRNA. We have shown that BAG-1 is highly expressed in a subset
of human invasive breast cancers and are now investigating the functional
and clinical significance of BAG-1 expression in breast cancer cells.
BCL-X We have investigated the mechanisms that control transcription
of BCL-XL. The long term goal is to use this information to interfere
with BCL-XL expression to promote cancer cell death. We have made several
important discoveries, including a powerful promoter that contributes
to BCL-XL expression in many cancer cell types and a novel pathway of
cytokine-dependent regulation of BCL-XL expression.
Translational research is a particular strength in Southampton, especially
in the areas of novel antibody therapy, DNA vaccines and the use of radioimmunotherapy
for lymphoma. Several immunotherapy reagents developed in Southampton
are in early phase clinical trials, with more being tested at the pre-clinical
stage.
Clinical research includes all tumour types, with particular expertise
in malignant lymphoma and testicular cancer. 400 patients enter into phase
I, II and III trials each year. Members of the unit lead national studies
in lymphoma and germ cell tumours and we are developing the next generation
of trials in Hodgkin's disease and Burkitt's lymphoma. We are taking a
leading role in the UK studies of the novel monoclonal antibody Hu1D10
and the radioimmunotherapy reagent Ibritumomab-tiuxetan, both for lymphoma.
The EORTC study of chemotherapy and surgery for liver metastases is coordinated
for the UK in Southampton.
