Autologous dendritic cell vaccines for non-small-cell lung cancer.
OBJECTIVE
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.


CONCLUSIONS
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.
Hirschowitz
Edward A
EA
Division of Pulmonary and Critical Care Medicine, University of Kentucky, Chandler Medical Center, 800 Rose Street, Room MN 614, Lexington, KY 40536, USA. eahirs2@pop.uky.edu
Foody
Terry
T
Kryscio
Richard
R
Dickson
Larry
L
Sturgill
Jamie
J
Yannelli
John
J
D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome
D019496:Cancer Vaccines