A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late-stage lung carcinoma.
BACKGROUND
The authors conducted a pilot clinical trial to explore the vaccination of patients with late-stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy.


METHODS
Autologous DCs were generated by culturing adherent mononuclear cells with interleukin-4 and granulocyte-macrophage-colony-stimulating factor for 7 days. Day-7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor-alpha for 16 hours. The antigen-loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late-stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly.


RESULTS
The authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T-cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T-cell responses.


CONCLUSIONS
The results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T-cell responses and provide clinical benefit in some patients.
Chang
Gee-Chen
GC
Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Lan
Haw-Chang
HC
Juang
Shin-Hun
SH
Wu
Yu-Chen
YC
Lee
Hui-Chen
HC
Hung
Yi-Mei
YM
Yang
Hui-Yu
HY
Whang-Peng
Jacqueline
J
Liu
Ko-Jiunn
KJ
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016066:Pleural Effusion, Malignant / Q000166:cytology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor