This project comprises an attempt to generate and validate methodology for treatment of Ewing’s Sarcoma patients with specific targeted immunotherapy. Immunotherapy is the manipulation of the patient’s own immune system to recognise cancer as “foreign” as opposed to “self”. Although cancer vaccines and immune manipulation have been tried in cancer patients for many years without the dramatic clinical successes observed with chemotherapy, the field is yet to benefit from the molecular advances in understanding of immunology and the powerful techniques of gene therapy.

The concept of this application is that Ewing’s Sarcoma cells express a protein (PAX3) which is present at high levels and needed for the cancerous process. PAX3 however is absent from normal body tissues because its normal function is largely restricted to a few days of early embryonic development. We have recently shown, in a patient with Ewing’s Sarcoma that we have treated with non-targeted immunutherapy, that a component of the anti-tumour immune response was specifically directed at the PAX3 protein in the tumour. This cofirms our laboratory findings indicating that it is possible to make strong immune responses against PAX3 from normal blood cells including the blood cells of patients with cancer.

In this project we will make strong immune responses against PAX3 from normal blood cells in the laboratory. Once the cells responsible for the highest degree of tumour specific killing have been isolated, the PAX3 killing genes from the killer cells will be cloned. These genes will be tranferred into viruses and the viruses used to infect normal immune killer cells from patients with Ewing’s Sarcoma or similar PAX3 expressing tumours. The infected cells should adopt new killing behaviour directed specifically against PAX3 expressing tumour cells. Once validated these viruses will be suitable reagents for treatment of Ewing’s Sarcoma patients by gene therapy.

Dr John Anderson, Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, London