Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.
To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.
Mukherjee
Pinku
P
Mayo Clinic College of Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ 85259, USA.
Tinder
Teresa L
TL
Basu
Gargi D
GD
Pathangey
Latha B
LB
Chen
Lieping
L
Gendler
Sandra J
SJ
D000818:Animals; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000628:therapy*; D051379:Mice; D018396:Mucin-1 / Q000276:immunology*; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D018396:Mucin-1; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9