For instance, an early pre-clinical study using a monoclonal antibody against cytotoxic T lymphocyte antigen (CTLA)-4 in conjunction with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine found that initiation of the therapy within 4 days of intradermal challenge with a variant of the B16 cell line was able to control tumor growth while initiation of the therapy after 8 days was less effective and essentially ineffective after 12 days (van Elsas et al., 1999). This evidence concerns the gene CTLA4 and neoplasm.