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.
OBJECTIVE
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.


METHODS
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 alpha 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.
Liu
Ko-Jiunn
KJ
Cancer Research Cooperative Laboratory at the National Taiwan University Hospital, Division of Cancer Research, National Health Research Institutes, Taipei, Republic of China.
Wang
Chuan-Cheng
CC
Chen
Li-Tzong
LT
Cheng
Ann-Lii
AL
Lin
Dong-Tsamn
DT
Wu
Yu-Chen
YC
Yu
Wei-Lan
WL
Hung
Yi-Mei
YM
Yang
Hui-Yu
HY
Juang
Shin-Hun
SH
Whang-Peng
Jacqueline
J
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy*; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; C438506:HLA-A*24:02 antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D010455:Peptides; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor