title: 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.
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.
authors.affiliation: The University of Alabama at Birmingham, WTI 275-J2, 1530 Third Avenue South, Birmingham, AL 35294-3300, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Neidhart
authors.forename: Karen O
authors.initials: KO
authors.lastname: Allen
authors.forename: Daunte L
authors.initials: DL
authors.lastname: Barlow
authors.forename: Mark
authors.initials: M
authors.lastname: Carpenter
authors.forename: Denise R
authors.initials: DR
authors.lastname: Shaw
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D000917:Antibody Formation / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology*; D016367:Baculoviridae / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002455:Cell Division; D002626:Chemistry, Pharmaceutical; D015179:Colorectal Neoplasms / Q000276:immunology*; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D000071858:Epithelial Cell Adhesion Molecule; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008050:Lipid A / Q000737:chemistry*; D008081:Liposomes; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D008899:Mineral Oil; D010865:Pilot Projects; D011994:Recombinant Proteins; D012882:Skin Tests; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D004655:Emulsions; D000071858:Epithelial Cell Adhesion Molecule; D008050:Lipid A; D008081:Liposomes; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D016179:Granulocyte Colony-Stimulating Factor; D008899:Mineral Oil; D007371:Interferon-gamma