Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21.
Our objective was to determine whether an immune response can be generated against MUC1 peptide and against tumor cell MUC1 after vaccination with MUC1-keyhole limpet hemocyanin (KLH) conjugate plus QS-21 in breast cancer patients. Nine patients with a history of breast cancer but without evidence of disease were treated with MUC1-KLH conjugate plus QS-21, containing 100 microg of MUC1 and 100 microg of QS-21. s.c. vaccinations were administered at weeks 1, 2, 3, 7, and 19. Peripheral blood was drawn at frequent intervals to assess antibody titers. Skin tests were placed at weeks 1, 3, 9, and 21 to determine delayed type hypersensitivity reactions. Common toxicities included a local skin reaction at the site of the vaccine, usually of 4-5 days' duration, and mild flu-like symptoms usually of 1-2 days' duration. High IgM and IgG antibody titers against synthetic MUC1 were detected. IgG antibody titers remain elevated from a minimum of 106-137 weeks after the first vaccination. Binding of IgM antibody to MCF-7 tumor cells was observed in seven patients, although there was minimal binding of IgG antibody. Two patients developed significant antibody titers post-high-dose chemotherapy and stem cell reinfusion. There was no evidence of T cell activation. This MUC1-KLH conjugate plus QS-21 was immunogenic and well tolerated in breast cancer patients. Additional trials are ongoing to determine the optimal MUC1 peptide for use in larger clinical trials. Further investigation of vaccine therapy in high-risk breast cancer is warranted.
Gilewski
T
T
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Adluri
S
S
Ragupathi
G
G
Zhang
S
S
Yao
T J
TJ
Panageas
K
K
Moynahan
M
M
Houghton
A
A
Norton
L
L
Livingston
P O
PO
D000276:Adjuvants, Immunologic; D000328:Adult; D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood / Q000187:drug effects; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006433:Hemocyanins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007075:Immunoglobulin M / Q000097:blood / Q000187:drug effects; D008875:Middle Aged; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000906:Antibodies; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin