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Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non–Small-Cell Lung Cancer

From the Division of Hematology/Oncology, Department of Medicine, Department of Microbiology and Immunology, and Department of Epidemiology and Public Health, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL

Address reprint requests to Luis E. Raez, MD, FACP, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, 1475 NW 12 Ave # 3510, Miami, FL 33136; e-mail: lraez{at}med.miami.edu

PURPOSE: To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non–small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease.

PATIENTS AND METHODS: We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 x 10⁷ cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100.

RESULTS: Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response.

CONCLUSION: Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.

Supported by the Research Career Development Award given by the American Society of Clinical Oncology, University of Miami/WCA, RO1-CA39201-14, and the family of Iris Zeitler.

Preliminary results were presented at the 92nd Annual Meeting of the American Association of Cancer Research (AACR), San Francisco, CA, April 6–10, 2002, and the 10th World Conference on Lung Cancer, Vancouver, Canada, August 10–14, 2003.

In memory of Dr Kasi Sridhar (1953–2001).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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