Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A0201 and HLA-A2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides

• Published in: Clinical cancer research Vol. 10; no. 8; pp. 2645 - 2651
• Main Authors: LIU, Ko-Jiunn, WANG, Chuan-Cheng, WHANG-PENG, Jacqueline, CHEN, Li-Tzong, CHENG, Ann-Lii, LIN, Dong-Tsamn, WU, Yu-Chen, YU, Wei-Lan, HUNG, Yi-Mei, YANG, Hui-Yu, JUANG, Shin-Hun
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.04.2004
• Subjects: Adult; Aged; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines; Carcinoembryonic Antigen - immunology; Cells, Cultured; Colorectal Neoplasms - genetics; Colorectal Neoplasms - therapy; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Genotype; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; HLA-A Antigens - genetics; HLA-A2 Antigen; HLA-A24 Antigen; Humans; Immunotherapy - methods; Interferon-gamma - metabolism; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Peptides - chemistry; Peptides - therapeutic use; Pharmacology. Drug treatments; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Tumors; Human; Pulsed dendritic cell; HLA-System; Load; Late; Immune response; Peptides; Oncofetal antigen; Major histocompatibility system; Vaccination; Colorectal cancer; Prevention; Carcinoembryonic antigen; Immunoprophylaxis; HLA-A-Locus; Digestive diseases; Intestinal disease; Class I histocompatibility antigen
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0430

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.