Abstract 2423: Phase I/II study of antitumor vaccination using lung cancer cells expressing murine α(1,3)galactosyltransferase (αGT) in non-small cell lung cancer (NSCLC)
Authors: Morris John C. , Rossi Gabriela R. , Janik John E. , Harold Nancy , Pittaluga Stefania , Malyguine Anatoli , Strobl Susan , Tennant Lucinda , Vahanian Nicholas , Link Charles J. 
Published: February 2011

Abstract
Background: Alpha(1,3)-linked galactose (αGal) epitopes are immunogenic and mediate rejection of non-primate xenografts. Vaccination of αGal knockout mice with tumor expressing αGT stimulated immunity against αGal-negative tumor and induced rejection of tumor. We studied the safety and antitumor activity of a vaccine using allogeneic human NSCLC cells engineered to express murine αGT gene in patients with NSCLC. The vaccine is composed of equal numbers of three αGT transduced human NSCLC cell lines. Methods: Patients with metastatic or recurrent NSCLC, age ≥18, ECOG PS ≤2, ≤2 prior systemic therapies, adequate hematological, hepatic and renal function, and informed consent were eligible. In phase I cohorts of patients received intradermal injections totaling 3, 10, 30, or 100 × 10E+6 vaccine cells every 4-weeks x 4; or 500 × 10E+6 vaccine cells followed by 300 × 10E+6 vaccine cells every 2-weeks × 7. In Phase II, eligible patients received injections totaling 300 × 10E+6 vaccine cells every 2 weeks for 8 doses. Adverse events were assessed using CTC v3.0 and response was determined using modified RECIST criteria. Serum anti-αGal antibody titers were monitored and ELISPOT assays for induction of interferonγ and interleukin-5 by PBMC were examined pre- and post vaccination. Vaccine site biopsies were performed. Results: 17 patients were treated in phase I. No vaccine-related serious adverse events (AE) were observed. Related AE's were ≤CTC grade 2 and included injection site pain/discomfort, local hyperpigmentation, skin reactions, local urticaria, arthralgias/myalgias, dyspnea, fatigue, herpes zoster, hypertension, lymphopenia and mild serum transaminitis. Six patients experienced stable disease for ≥4.0 months (median 8.0, range, 6.0-63.1 months). In phase II, 23 patients treated, 16 patients received one and five patients received two prior treatment regimens and two patients had no prior treatment (one of those had surgery only). Seven patients demonstrated SD ≥4.0 months. Median survival for the entire group was 11.0 months (range, 2.1-35.7 months) and 23.7 months (range, 11.0-35.7 months) for patients that achieved SD. Vaccine sites demonstrated infiltration of lymphocytes, granulocytes and eosinophils. Anti-αGal titers increased in all patients, and release of interferonγ and interleukin-5 during co-culture with vaccine parental and an unrelated NSCLC cell line was detected in some patients. Increases in anti-CEA antibodies were also detected. Conclusions: Antitumor vaccination using genetically altered human lung cancer cells expressing αGT is safe and feasible. A number of patients had prolonged SD and the median survival of vaccinated patients compared favorably to that reported in patients receiving 2nd line chemotherapy for relapsed or progressive advanced NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2423.