Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A*0201 and HLA-A*2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides

Ko Jiunn Liu, Chuan Cheng Wang, Li Tzong Chen, Ann Lii Cheng, Dong Tsamn Lin, Yu Chen Wu, Wei Lan Yu, Yi Mei Hung, Hui Yu Yang, Shin Hun Juang, Jacqueline Whang-Peng

Research output: Contribution to journalArticle

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Abstract

Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.

Original languageEnglish
Pages (from-to)2645-2651
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number8
DOIs
Publication statusPublished - Apr 15 2004
Externally publishedYes

Fingerprint

HLA-A Antigens
Carcinoembryonic Antigen
Dendritic Cells
Colorectal Neoplasms
Vaccination
T-Lymphocytes
Peptides
Genotype
HLA-A*02:01 antigen
Groin
Granulocyte-Macrophage Colony-Stimulating Factor
Autoimmunity
Interleukin-4
Research Design
Therapeutics
Tumor Necrosis Factor-alpha
Lymph Nodes
Safety
Drug Therapy
Injections

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A*0201 and HLA-A*2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides. / Liu, Ko Jiunn; Wang, Chuan Cheng; Chen, Li Tzong; Cheng, Ann Lii; Lin, Dong Tsamn; Wu, Yu Chen; Yu, Wei Lan; Hung, Yi Mei; Yang, Hui Yu; Juang, Shin Hun; Whang-Peng, Jacqueline.

In: Clinical Cancer Research, Vol. 10, No. 8, 15.04.2004, p. 2645-2651.

Research output: Contribution to journalArticle

Liu, Ko Jiunn ; Wang, Chuan Cheng ; Chen, Li Tzong ; Cheng, Ann Lii ; Lin, Dong Tsamn ; Wu, Yu Chen ; Yu, Wei Lan ; Hung, Yi Mei ; Yang, Hui Yu ; Juang, Shin Hun ; Whang-Peng, Jacqueline. / Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A*0201 and HLA-A*2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 8. pp. 2645-2651.
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abstract = "Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70{\%}) patients. Two (20{\%}) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.",
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T1 - Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A*0201 and HLA-A*2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides

AU - Liu, Ko Jiunn

AU - Wang, Chuan Cheng

AU - Chen, Li Tzong

AU - Cheng, Ann Lii

AU - Lin, Dong Tsamn

AU - Wu, Yu Chen

AU - Yu, Wei Lan

AU - Hung, Yi Mei

AU - Yang, Hui Yu

AU - Juang, Shin Hun

AU - Whang-Peng, Jacqueline

PY - 2004/4/15

Y1 - 2004/4/15

N2 - Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.

AB - Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.

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JF - Clinical Cancer Research

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