Induction of MUC1-specific cellular immunity by a recombinant BCG expressing human MUC1 and secreting IL2.
MUC1 mucin is aberrantly expressed in many epithelial malignancies and is a promising tumor antigen for target-directed immunotherapy against human breast cancer. Mycobacterium BCG is an effective immunoadjuvant which is known to induce Th1 immune response. Recombinant BCG expressing tumor antigen and secreting cytokine may therefore potentiate the tumor antigen-specific immune responses. In this study, we constructed a recombinant BCG-MUC1-IL2, which expresses a high level of human MUC1 VNTR core protein and secretes functional interleukin 2 (IL2). The immune responses induced by BCG-MUC1-IL2 were examined using a SCID mouse model reconstituted with immunologically competent human lymphocytes, SCID/hu-PBL. The mucin-specific IFN-gamma was secreted only by the lymphocytes derived from animals immunized with BCG-MUC1-IL2, but not with BCG-vector or purified mucin protein for the vaccination. In contrast, in vitro secretion of IL4 by the immunized lymphocytes was only seen in the group of animals which received native MUC1 protein, but not BCG-MUC1-IL2 and BCG-vector. Minimal MUC1-specific IgG and IgM were detected in SCID/hu-PBL mice vaccinated with BCG-MUC1-IL2. These results suggest that BCG-MUC1-IL2 preferentially induces MUC1-specific cellular immune responses and it may serve as a vaccine for breast cancer prevention and treatment.
He
Jianbo
J
Revlon/UCLA Breast Center, Department of Surgery, University of California at Los Angeles, School of Medicine, 90095, USA.
Shen
Dejun
D
O'Donnell
Michael A
MA
Chang
Helena R
HR
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D019496:Cancer Vaccines; D007376:Interleukin-2; D018396:Mucin-1; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D007371:Interferon-gamma