1. Immunization of colorectal cancer patients with recombinant baculovirus-derived KSA (Ep-CAM) formulated with monophosphoryl lipid A in liposomal emulsion, with and without granulocyte-macrophage colony-stimulating factor.
- Author
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Neidhart J, Allen KO, Barlow DL, Carpenter M, Shaw DR, Triozzi PL, and Conry RM
- Subjects
- Adult, Aged, Antibodies, Neoplasm analysis, Antibodies, Neoplasm biosynthesis, Antibody Formation immunology, Antigen-Antibody Reactions, Cancer Vaccines adverse effects, Cell Division, Chemistry, Pharmaceutical, Emulsions, Enzyme-Linked Immunosorbent Assay, Epithelial Cell Adhesion Molecule, Escherichia coli immunology, Female, Humans, Immunity, Cellular immunology, Immunization, Interferon-gamma biosynthesis, Liposomes, Lymphocyte Count, Male, Middle Aged, Mineral Oil, Pilot Projects, Recombinant Proteins, Skin Tests, Vaccines, Synthetic immunology, Adjuvants, Immunologic pharmacology, Antigens, Neoplasm immunology, Baculoviridae immunology, Cancer Vaccines immunology, Cell Adhesion Molecules immunology, Colorectal Neoplasms immunology, Granulocyte Colony-Stimulating Factor pharmacology, Lipid A chemistry
- Abstract
KSA (Ep-CAM) is highly expressed by colorectal cancers. The safety and immunologic effects of a vaccine consisting of recombinant baculovirus-derived KSA formulated with monophosphoryl lipid A (MPL) in liposomes and emulsified in mineral oil were evaluated, with and without co-administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). Eleven patients with metastatic colorectal cancer received three subcutaneous (s.c.) injections of the vaccine at 4-week intervals. Six patients were randomized to also receive human recombinant GM-CSF (rGM-CSF) by subcutaneous injection daily for 4 days with each vaccination. Immunizations with and without rGM-CSF were well tolerated. Seven of the 11 patients developed significant KSA-specific cellular immune responses as assessed by lymphoproliferation and interferon-gamma (IFN-gamma) ELISPOT assays. All nine tested patients developed positive delayed type hypersensitivity reactions. Eight of the 11 patients developed KSA-specific antibody responses. The highest levels of cellular immune responses were observed in patients who received GM-CSF. Immunization with baculovirus-derived KSA formulated with monophosphoryl lipid A in liposomal emulsion is safe and can elicit KSA-specific immune responses. Co-administration of GM-CSF with this formulation is an effective method of generating KSA-specific T-helper (Th) 1-associated cellular immune responses.
- Published
- 2004
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