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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Published on: January 6, 2014
Autologous dendritic cell vaccines for non-small-cell lung cancer
Edward A Hirschowitz1, Terry Foody, Richard Kryscio
1Division 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
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.
Insights
Dendritic cell (DC) vaccines were well-tolerated and showed biologic activity in non-small cell lung cancer (NSCLC) patients. Further studies are needed to optimize DC vaccine therapy for NSCLC.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Therapeutic outcomes for non-small cell lung cancer (NSCLC) remain poor.
- Dendritic cell (DC) vaccines show preclinical and some clinical promise for cancer therapy.
- Limited clinical data exists on DC vaccines in NSCLC patients.
Purpose of the Study:
- To evaluate the tolerability of autologous DC vaccines in NSCLC patients.
- To measure immunologic responses to DC vaccines in a heterogeneous NSCLC patient group.
- To assess the safety and biologic activity of DC vaccines in NSCLC.
Main Methods:
- DC vaccines were generated from CD14+ precursors and pulsed with allogeneic NSCLC cell line apoptotic bodies overexpressing specific tumor antigens.
- DCs were partially matured to induce surface molecule expression with minimal cytokine production.
- Patients received two intradermal immunizations one month apart, with immune responses monitored via interferon-gamma ELISPOT assays.
Main Results:
- No serious adverse events were observed, indicating good tolerability.
- Immunologic responses varied: 5/16 showed no response, 5/16 showed tumor-antigen independent response, and 6/16 demonstrated antigen-specific responses.
- Immunologic responses and clinical outcomes were independent of NSCLC stage and prior therapy.
Conclusions:
- Autologous DC vaccines were well-tolerated and demonstrated biologic activity across a range of NSCLC patients.
- Further comparative studies in well-defined NSCLC patient groups are necessary to establish optimal DC vaccine approaches.
- DC vaccines represent a potential therapeutic strategy for NSCLC, warranting further investigation.
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