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A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four α-Fetoprotein Peptides

BUTTERFIELD, Lisa H ; RIBAS, Antoni ; MCBRIDE, William H ; FINN, Richard ; GLASPY, John A ; ECONOMOU, James S ; DISSETTE, Vivian B ; LEE, Yohan ; JIN QUAN YANG ; DE LA ROCHA, Pilar ; DURAN, Sonia D ; HERNANDEZ, Jackie ; SEJA, Elisabeth ; POTTER, Douglas M

Clinical cancer research, 2006-05, Vol.12 (9), p.2817-2825 [Periódico revisado por pares]

Philadelphia, PA: American Association for Cancer Research

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Título:
A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four α-Fetoprotein Peptides
Autor: BUTTERFIELD, Lisa H ; RIBAS, Antoni ; MCBRIDE, William H ; FINN, Richard ; GLASPY, John A ; ECONOMOU, James S ; DISSETTE, Vivian B ; LEE, Yohan ; JIN QUAN YANG ; DE LA ROCHA, Pilar ; DURAN, Sonia D ; HERNANDEZ, Jackie ; SEJA, Elisabeth ; POTTER, Douglas M
Assuntos: Adult ; Aged ; alpha-Fetoproteins - therapeutic use ; alpha-Fetoproteins - toxicity ; Amino Acid Sequence ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - therapy ; clinical trial ; dendritic cells ; Dendritic Cells - transplantation ; Disease Progression ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; immunotherapy ; Liver Neoplasms - immunology ; Liver Neoplasms - therapy ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Middle Aged ; Peptide Fragments - therapeutic use ; Peptide Fragments - toxicity ; Pharmacology. Drug treatments ; T lymphocytes ; Tumors ; α-Fetoprotein
É parte de: Clinical cancer research, 2006-05, Vol.12 (9), p.2817-2825
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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Descrição: α-Fetoprotein (AFP) is a self protein expressed by fetal liver at high levels, but is transcriptionally repressed at birth. AFP is up-regulated in hepatocellular carcinomas, and patients with active disease could have plasma levels as high as 1 mg/mL. We previously identified four immunodominant HLA-A*0201-restricted peptides [hAFP 137-145 (PLFQVPEPV), hAFP 158-166 (FMNKFIYEI), hAFP 325-334 (GLSPNLNRFL), and hAFP 542-550 (GVALQTMKQ)] derived from human AFP that could stimulate specific T cell responses in healthy donor peripheral blood lymphocytes in vitro . We conducted a phase I/II clinical trial in which HLA-A*0201 patients with AFP-positive hepatocellular carcinoma were immunized with three biweekly intradermal vaccinations of the four AFP peptides pulsed onto autologous dendritic cells (DC). DCs were prepared from adherent peripheral blood mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. Sixteen subjects were enrolled and 10 were treated. Peripheral blood lymphocytes were isolated from these patients before, during, and after AFP peptide/DC immunization and were tested ex vivo with MHC tetramer and IFNγ ELISPOT analysis. Six of 10 subjects expanded statistically significant levels of AFP-specific T cells postvaccine to at least one peptide by MHC tetramer. Also, 6 of 10 subjects increased IFNγ producing AFP-specific T cell responses to at least one of the peptides postvaccination, by ELISPOT. We conclude that the human T cell repertoire is capable of responding to the AFP self antigen after the administration of AFP peptide-pulsed DC even in an environment of high circulating levels of this oncofetal antigen.
Editor: Philadelphia, PA: American Association for Cancer Research
Idioma: Inglês

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A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four α-Fetoprotein Peptides

BUTTERFIELD, Lisa H ; RIBAS, Antoni ; MCBRIDE, William H ; FINN, Richard ; GLASPY, John A ; ECONOMOU, James S ; DISSETTE, Vivian B ; LEE, Yohan ; JIN QUAN YANG ; DE LA ROCHA, Pilar ; DURAN, Sonia D ; HERNANDEZ, Jackie ; SEJA, Elisabeth ; POTTER, Douglas M

Philadelphia, PA: American Association for Cancer Research

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