Autologous dendritic cell vaccines for non-small-cell lung cancer
ABSTRACT
PURPOSE: Therapeutic outcomes of definitively treated non-small-cell lung cancer (NSCLC) are unacceptably poor. A wealth of preclinical information, and a modest amount of clinical information indicate that dendritic cell (DC) vaccines have therapeutic potential. Only a handful of NSCLC patients have been included in DC clinical trials. We delivered autologous DC vaccines to 16 individuals with stage IA to IIIB NSCLC treated with surgery, chemoradiation, or multimodality therapy. The objectives of the study were to evaluate tolerability and measure immunologic responses to DC vaccines in a heterogeneous group of NSCLC patients.
METHODS: DC vaccines were generated from CD14+ precursors, pulsed with apoptotic bodies of an allogeneic NSCLC cell line that overexpressed Her2/neu, CEA, WT1, Mage2, and survivin. DCs were partially matured with a factor that induced surface molecule expression but minimal cytokine production. Individuals were immunized intradermally two times, 1 month apart. Peripheral blood was drawn serially over 16 weeks, and immune responses were measured by interferon-gamma ELISPOT.
RESULTS: There were no unanticipated or serious adverse events. Immunologic responses followed three distinct patterns of reactivity: (1) five of 16 patients showed no clear immunologic response, (2) five of 16 patients showed a tumor-antigen independent response, and (3) six of 16 show an antigen specific response. Immunologic responses were independent of stage and prior therapy. Favorable and unfavorable clinical outcomes were independent of measured immunologic responses.
CONCLUSION: Vaccines were well tolerated and had biologic activity in a variety of NSCLC patients. Establishing an optimal approach will require comparative studies in well-defined NSCLC patient groups.