Phase II trial of a GM-CSF-producing and CD40L-expressing bystander cell line combined with an allogeneic tumor cell-based vaccine for refractory lung adenocarcinoma

• Published in: Journal of immunotherapy (1997) Vol. 36; no. 8; pp. 442 - 450
• Main Authors: Creelan, Ben C, Antonia, Scott, Noyes, David, Hunter, Terri B, Simon, George R, Bepler, Gerold, Williams, Charles C, Tanvetyanon, Tawee, Haura, Eric B, Schell, Michael J, Chiappori, Alberto
• Format: Journal Article
• Language: English
• Published: United States 01-10-2013
• Subjects: Adenocarcinoma; Adenocarcinoma - immunology; Adenocarcinoma - mortality; Adenocarcinoma - therapy; Aged; Antigen Presentation; Antigens, Neoplasm - immunology; Bystander Effect; Cancer Vaccines; CD40 Ligand - genetics; CD40 Ligand - metabolism; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - drug effects; Dendritic Cells - immunology; Female; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; K562 Cells; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Lymphocyte Activation; Male; Middle Aged; Neoplasm Metastasis; Recurrence; Survival Analysis; Transgenes - genetics; Treatment Outcome; Tretinoin - administration & dosage
• ISSN: 1524-9557; 1537-4513
• DOI: 10.1097/CJI.0b013e3182a80237

We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized that the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given q14 days×3, followed by monthly ×3. Cyclophosphamide (300 mg/m IV) was administered before the first and fourth vaccines to deplete regulatory T cells. All-trans retinoic acid was given (150/mg/m/d) after the first and fourth vaccines to enhance dendritic cell differentiation. Twenty-four participants were accrued at a single institution from October 2006 to June 2008, with a median age 64 years and median of 4 previous lines of systemic therapy. A total of 101 vaccines were administered. Common toxicities were headache (54%) and site reaction (38%). No radiologic responses were observed. Median overall survival was 7.9 months and median progression-free survival was 1.7 months. Of 14 patients evaluable for immunological study, 5 had peptide-induced CD8 T-cell activation after vaccination. Overall, vaccine administration was feasible in an extensively pretreated population of metastatic lung cancer. Despite a suggestion of clinical activity in the subset with immune response, the trial did not meet the primary endpoint of inducing radiologic tumor regression.