Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide.
Sixteen metastatic breast cancer patients were immunized with a low dose (5 micrograms) of a 16 amino acid MUC1 peptide (GVTSAPDTRPAPGSTA) conjugated to KLH (BP16-KLH) plus DETOX adjuvant and evaluated for antibody titers against MUC1 peptide and KLH and for cytotoxic lymphocyte (CTL) activity using class 1 HLA-matched MUC1-positive tumor targets. All patients generated strong anti-KLH IgG responses. Only 3 patients developed an anti-MUC1 IgG response, which was weak in magnitude. As it is controversial whether human cancer patients generate class-1-restricted CTL against MUC1, we examined anti-MUC1 CTL activity of PBLs following 4 immunizations with BP16-KLH. The generation of MUC1-specific CTLs required only a 6-day in vitro stimulation of patients' T-cells with synthetic MUC1-peptide-pulsed autologous APCs. The assay for CTL activity was a 4 hour 51Cr release from labeled adenocarcinoma target cells. Eleven of the 16 immunized patients were tested for CTL activity using class-1-matched adenocarcinoma target cell lines. Evidence for class-1-restricted killing of MUC1-expressing tumor cell lines was obtained in 7 of these 11 patients.
Reddish
M
M
ID Vaccine, Bothell, WA, USA.
MacLean
G D
GD
Koganty
R R
RR
Kan-Mitchell
J
J
Jones
V
V
Mitchell
M S
MS
Longenecker
B M
BM
D001943:Breast Neoplasms / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D018396:Mucin-1 / Q000276:immunology*; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D018396:Mucin-1