Complete molecular remissions induced by patient-specific vaccination plus granulocyte–monocyte colony-stimulating factor against lymphoma

Abstract

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. 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-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

Variations in “rescuability” of immunoglobulin molecules from different forms of human lymphoma: implications for anti-idiotype vaccine development

“…It is also noteworthy that both the fusion-related and the overall feasibility of the Id vaccine treatment for FL in first relapse were comparable with those already described for both newly diagnosed and relapsed patients with the same disease [6,7]. In our series, one FL patient experienced both pre-vaccine disease progression and failure to produce an Id vaccine.…”

“…1; [3,4]). Subsequently, it was shown that immunization of FL patients against such a self-antigen was possible [5] and induced an idiotype-specific, humoral [5][6][7][8] and cellular [6,7,9] immune response. Finally, it was demonstrated that in vivo, vaccine-induced, Id-specific immune responses can kill FL cells that have survived standard chemotherapy (CHT; [7,8]).…”

Anti-idiotype antibodies in cancer treatment

“…Even more importantly, most tested patients with MRD after CHT and before vaccination had their MRD cleared upon completion of the vaccination schedule. In other words, this study showed that tumor cells that had survived CHT were indeed killed by immune effector mechanisms induced through vaccination (Bendandi et al, 1999). Similar results were later reproduced on a smaller scale by scientists at the Puerta de Hierro Hospital of Madrid (Barrios et al, 2002).…”

Cloning of B cell lymphoma-associated antigens using modified phage-displayed expression cDNA library and immunized patient sera

“…Following informed consent, sera were taken from patients who had a positive clinical response in the ongoing idiotype vaccine trial for follicular B cell lymphoma at the National Cancer Institute (Bendandi et al, 1999). Prevaccine and postvaccine sera from patients or serum from healthy donors were diluted 1:10 and pre-absorbed by repeated passing on a Sepharose 4B column coupled with the lysate from BLT5615 E. coli infected with T7 phage.…”

“…However, the majority of antigens have been cloned from solid tumors, while almost no TAAs were reported to date for hematopoietic malignancies. B cell lymphoma-specific antigens are not defined, except for immunoglobulin, idiotype (Id), which is being successfully used for immunotherapy of patients with follicular lymphoma (Bendandi et al, 1999). It is presumed that CT antigens would not be good markers for B cell malignancies, such as non-Hodgkin's lymphomas and myeloma (Xie et al, 2003), since only a small proportion of B cells express CT antigens (Huang et al, 2002).…”