A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma.

Clinical studies suggest that treatment with vaccines comprised of idiotype protein may be associated with improved clinical outcome in follicular lymphoma patients. The time-consuming process required to generate patient-specific vaccines is a major limitation, however. Here we report results of a pilot clinical trial with a novel autologous, tumor-derived proteoliposome vaccine formulation that could be rapidly produced within a single day. Vaccination was safe, induced autologous tumor-specific type 1 cytokine responses in 5 out of 10 follicular lymphoma patients, and was associated with induction of a sustained complete response in one patient. Other patients had large tumor burdens and progressed after a median duration of 8 months. These results suggest that further testing of this vaccine formulation, particularly in the setting of minimal disease, is warranted. Furthermore, the proteoliposome formulation may provide a model for vaccine development for other human cancers, for which tumor-associated antigens need not be defined.

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

PURPOSE: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. EXPERIMENTAL DESIGN: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. RESULTS: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. CONCLUSIONS: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8+ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.