Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX® vaccine in advanced-stage non-small-cell lung cancer

Abstract

Tumor vaccines composed of autologous tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) (GVAX s ) have demonstrated clinical activity in advanced-stage non-small-cell lung cancer (NSCLC). In an effort to remove the requirement for genetic transduction of individual tumors, we developed a 'bystander' GVAX s platform composed of autologous tumor cells mixed with an allogeneic GM-CSF-secreting cell line. We conducted a phase I/II trial of this vaccine (3-12 biweekly vaccinations) in advanced-stage NSCLC. Tumors were harvested from 86 patients, tumor cell processing was successful in 76, and 49 proceeded to vaccination. The most common toxicity was local vaccine injection site reactions. Serum GM-CSF pharmacokinetics were consistent with secretion of GM-CSF from vaccine cells for up to 4 days with associated transient leukocytosis confirming the bioactivity of vaccine-secreted GM-CSF. Evidence of vaccine-induced immune activation was demonstrated; however, objective tumor responses were not seen. Compared with autologous GVAX s vaccines prepared by transduction of individual tumors with an adenoviral GM-CSF vector, vaccine GM-CSF secretion was approximately 25-fold higher with the bystander GVAX s vaccine used in this trial. However, the frequency of vaccine site reactions, tumor response, time to disease progression, and survival were all less favorable in the current study.

Lung cancer patients’ CD4+ T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells

“…GM-CSF-transduced autologous NSCLC cells induced a 10% response rate in advanced stage patients [27]. However, this treatment may not be practical for large numbers of patients because it requires the transduction of individual patients' tumor cells [26]. More promising is a vaccine generated by transfecting allogeneic NSCLC cells with the costimulatory molecule CD80 [30,31].…”

Vaccines for the Treatment of Non-Small Cell Lung Cancer: A Renewed Anticancer Strategy

“…Compared with autologous GVAX vaccines, vaccine GM-CSF secretion was approximately 25-fold higher with the bystander GVAX vaccine used in this trial. However, the frequency of vaccine site reaction, tumor response, TTP, and OS time were all less favorable in this study [55].…”

Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-β

“…However, in spite of the initial expectations, many genetic immunotherapy protocols have also failed to show significant results in the clinical setting. 3,4,[24][25][26] The absence or paucity of tumor antigens and inadequate immune stimuli might be, in part, the reasons for previous failures.…”