Complete molecular remissions induced by patient-specific vaccination plusgranulocyte-monocyte colony-stimulating factor against lymphoma

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein Vaccine for mulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 1 1 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosi s and after chemotherapy, despite being in complete remission. However, 8 o f 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular rem issions. Tumor-specific cytotoxic CD8(+) and CD4(+) T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-fr ee survival. The demonstration of molecular remissions, analysis of cytotox ic T lymphocytes against autologous tumor targets, and addition of granuloc yte-monocyte colony-stimulating factor to the vaccine formulation provide p rinciples relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.