A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma

Abstract

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 10⁶ or 1 × 10⁷ GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 10⁵ to 5 × 10⁷.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.

Keywords: Follicular lymphoma; GM-CSF; GVAX; immunotherapy; vaccine.