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

PMID: 15102666
Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (volume: 10, issue: 8, Clin. Cancer Res. 2004 Apr;10(8):2645-51)
Published: 2004-04-15

Authors:
Liu KJ, Wang CC, Chen LT, Cheng AL, Lin DT, Wu YC, Yu WL, Hung YM, Yang HY, Juang SH, Whang-Peng J

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 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.