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

Gee Chen Chang, Haw Chang Lan, Shin Hun Juang, Yu Chen Wu, Hui Chen Lee, Yi Mei Hung, Hui Yu Yang, Jacqueline Whang-Peng, Ko Jiunn Liu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalCancer
Volume103
Issue number4
DOIs
Publication statusPublished - Feb 15 2005
Externally publishedYes

Fingerprint

Malignant Pleural Effusion
Dendritic Cells
Vaccination
Clinical Trials
Carcinoma
Lung
Neoplasms
Neoplasm Antigens
Pleural Effusion
T-Lymphocytes
Groin
Granulocyte-Macrophage Colony-Stimulating Factor
Autoimmunity
Interleukin-4

Keywords

  • Dendritic cell
  • Immunotherapy
  • Nonsmall cell lung carcinoma
  • Pleural effusion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Chang, Gee Chen; Lan, Haw Chang; Juang, Shin Hun; Wu, Yu Chen; Lee, Hui Chen; Hung, Yi Mei; Yang, Hui Yu; Whang-Peng, Jacqueline; Liu, Ko Jiunn.

In: Cancer, Vol. 103, No. 4, 15.02.2005, p. 763-771.

Research output: Contribution to journalArticle

Chang, Gee Chen ; Lan, Haw Chang ; Juang, Shin Hun ; Wu, Yu Chen ; Lee, Hui Chen ; Hung, Yi Mei ; Yang, Hui Yu ; Whang-Peng, Jacqueline ; Liu, Ko Jiunn. / 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. In: Cancer. 2005 ; Vol. 103, No. 4. pp. 763-771.
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AU - Juang, Shin Hun

AU - Wu, Yu Chen

AU - Lee, Hui Chen

AU - Hung, Yi Mei

AU - Yang, Hui Yu

AU - Whang-Peng, Jacqueline

AU - Liu, Ko Jiunn

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N2 - 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.

AB - 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.

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