Current cancer vaccine approaches usually focus on therapeutic vaccines since autoimmune complications are a concern in the preventive setting. Now, reporting in Nature Medicine, Jaini and colleagues present a proto-typical strategy for the development of a prophylactic breast cancer vaccine. This is based on α-lactalbumin, a breast-specific differentiation antigen that is normally only expressed during lactation, but is present in the majority of human breast carcinomas.

To test whether the vaccination with α-lactalbumin could induce an immune response, female mice were immunized with a single dose of recombinant α-lactalbumin mixed with complete Freund’s adjuvant (CFA), or were given CFA alone. Non-lactating mice and mice immunized with CFA alone did not show any signs of autoimmunity, whereas lactating mice immunized with α-lactalbumin developed breast failure, defined as being unable to feed their pups.

The vaccine was then tested in mouse mammary tumour virus (MMTV)-neu mice, which spontane-ously develop mammary tumours. At 8 weeks of age mice were immunized with a single dose of α-lactalbumin plus CFA or given CFA alone. Whereas all CFA-only control mice developed breast tumours by the age of 10 months, none of the α-lactalbumin immu-nized mice had detectable tumours. Prophylactic vaccination was also shown to be effective against

transplantable tumours in wild-type mice, in which immunization 13 days before tumour cell inoculation resulted in significant tumour growth retardation.

To test the vaccine in the thera-peutic setting, wild-type mice were immunized 5 days or 13 days after tumour cell inoculation. Tumours from mice treated with α-lactalbumin in CFA were significantly smaller than tumours from mice treated with CFA alone. Similarly, in MMTV-PyVT mice, which develop highly aggressive palpable tumours by 5 weeks of age, vaccination at 6 weeks of age resulted in significant tumour growth inhibition. Further examination of spontaneous and transplanted tumours from mice treated with α-lactalbumin showed inflammatory infiltrates of interferon-γ-producing CD4+ T cells and of cytotoxic CD8+ T cells, which were not detectable in CFA-immunized control mice.

These results show that vaccina-tion with α-lactalbumin can provide effective protection in mouse models of breast cancer and can slow tumour cell growth when administered thera-peutically. Importantly, vaccination provided protection in the absence of any detectable autoimmune-induced breast inflammation. The authors caution that there is still some controversy about the level of α-lactalbumin expression on human breast tumours, and the immuno-genicity of human α-lactalbumin remains to be evaluated more thor-oughly. Nevertheless, the conditional

and tissue-specific expression of lactation-specific antigens could provide a unique opportunity for targeted vaccination of women in their post-childbearing years, when lactation is avoidable and the risk of developing breast cancer is high.

Alexandra Flemming

ORIGINAL RESEARCH PAPER Jaini, R. et al. An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nature Med. 16, 799–803 (2010)

C A N C E R

Steps towards a prophylactic breast cancer vaccine

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NATure reVIeWS | Drug Discovery VoluMe 9 | AuguST 2010

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