1133. A Phase I Study of Antitumor Vaccination Using Genetically Modified Tumor Cells Expressing α(1,3)Galactosyltransferase in Patients with Refractory or Recurrent Non-Small Cell Lung Cancer (NSCLC): Preliminary Results

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Background: Despite new therapies lung cancer remains the leading cause of cancer death. In a phase I trial we examined the safety and feasibility of antitumor vaccination with three genetically altered human lung cancer cell lines (HyperAcute|[trade]| Lung Cancer Vaccine) engineered to express xenotransplantation antigens through retroviral transfer of the murine |[alpha]|(1,3)galactosyltrasferase gene in patients (Pts) with advanced NSCLC. Methods: Pts with stage IV, recurrent or refractory NSCLC, ECOG PS |[le]|2, |[le]|2 prior chemotherapies, adequate nutrition, bone marrow and organ function were eligible for the study. Cohorts of 3 Pts were scheduled to receive intrademal injections of 3 |[times]| |[Lgr]|6, 10 |[times]| 10|[Lgr]|6, 30 |[times]| 10|[Lgr]|6, or 100 |[times]| 10|[Lgr]|6 irradiated vaccine cells every 4-weeks |[times]| 4. Toxicity was assessed using standard criteria and response was determined by RECIST criteria. Immunological responses included anti-|[alpha]|Gal antibody titers, whole cell interferon-|[gamma]| ELISPOT and vaccine site skin biopsies. Results: To date, 9 Pts, 6 men and 3 women, median age 54 (range, 34-72 yrs.), median number of prior chemotherapies 1 (range, 1-2) were vaccinated with up to 30 |[times]| 10|[Lgr]|6 cells. Five Pts received 4/4 vaccinations, 1 Pt received 3/4 vaccinations and 1 Pt received 2/4 vaccinations, and 2 Pts. have received 1 vaccination. Adverse events (|[le]|grade 2) attributable to vaccination include injection site pain/discomfort, local skin reaction, fatigue, and hypertension. Other adverse events (|[le]|grade 2) include bradycardia, cough, diarrhea, dyspnea, headache, hyperglycemia, hyponatremia, nausea, pleural effusion, and vomiting. Four patients had stable disease |[ge]|16 weeks (range, 21-36+ weeks), three other Pts progressed and 2 Pts are not evaluable at this time. Skin biopsies 48-hrs after vaccination demonstrated vaccine cells in the dermis with infiltration of lymphocytes and eosinophils. Conclusions: Antitumor vaccination with genetically altered allogeneic human lung cells expressing |[alpha]|(1,3) galactosyltrasferase is safe and feasible.