Although vaccination is most effective when used to prevent disease,
cancer vaccine development has focused predominantly on providing
therapy against established growing
tumors. The difficulty in developing prophylactic
cancer vaccines is primarily due to the fact that
tumor antigens are variations of self
proteins and would probably mediate profound autoimmune complications if used in a preventive
vaccine setting. Here we use several mouse
breast cancer models to define a prototypic strategy for prophylactic
cancer vaccination. We selected
alpha-lactalbumin as our target
vaccine autoantigen because it is a breast-specific differentiation
protein expressed in high amounts in the majority of human
breast carcinomas and in mammary epithelial cells only during lactation. We found that immunoreactivity against
alpha-lactalbumin provides substantial protection and
therapy against growth of autochthonous
tumors in transgenic mouse models of
breast cancer and against 4T1 transplantable
breast tumors in BALB/c mice. Because
alpha-lactalbumin is conditionally expressed only during lactation, vaccination-induced prophylaxis occurs without any detectable
inflammation in normal nonlactating breast tissue. Thus,
alpha-lactalbumin vaccination may provide safe and effective protection against the development of
breast cancer for women in their post-child-bearing, premenopausal years, when lactation is readily avoidable and risk for developing
breast cancer is high.