Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7

Background-The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed an 70-80% of colorectal cancers. Pha se I studies have shown that the vaccine is non-toxic, and a number of pati ents have been immunised prior to resection of their primary tumours. Aims-To assess lymphocyte activation at the tumour site by measuring expres sion of the alpha subunit of the interleukin 2 receptor (CD25). Methods-Nineteen patients with primary colorectal cancer were immunised wit h varying doses of 105AD7 prior to resection of their primary tumours. Samp les of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. S amples from a matched control group were also stained. Fresh tumours from 1 4 immunised patients and 31 unimmunised control patients were disaggregated , and the lymphocytes obtained labelled for CD25. Samples were analysed bli ndly by how cytometry. Results-Median infiltration of lymphocytes expressing CD25, measured immuno histochemically, was higher in trial patients, as was the ratio of tumour t o normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unma tched controls. Discussion-The alpha subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.