Experimental Vaccine Shields Mice From Breast Cancer

The vaccine, which sensitizes the immune system to a protein present only in breast cancer cells and normal lactating breast cells, was conceived by immunologists at the Cleveland Clinic’s Lerner Research Institute in Cleveland, Ohio, and was published in the journal Nature Medicine.
   
“We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines have prevented many childhood diseases,” said lead investigator Vincent Tuohy. “If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer.”

The vaccine targets α-lactalbumin, a protein found in the majority of breast cancers, and only present in healthy women when they are lactating, that is when their breasts are producing milk.

The challenge of developing a vaccine against cancer is that cancer is not like a virus that the immune system readily recognizes as alien: cancer cells are no more than over-produced variations of healthy cells, and trying to vaccinate against cancer cells risks destroying healthy tissue as well.

The key is therefore to find something that is present in and necessary for cancer cells to survive, but targeting it does not wipe out healthy cells at the same time: it revs up the immune system, but only targets the protein necessary for tumor formation.

So Tuohy and colleagues decided to try for α-lactalbumin, because this would fit with a strategy of vaccinating women over 40, when breast cancer risk begins to rise and pregnancy is less likely. (They explained that if a woman receiving this vaccine did fall pregnant then her breasts would feel sore and she would probably have to opt not to breast feed).

For the study, they tested the effect of the vaccine in mice genetically bred to be prone to breast cancer: usually such mice develop breast tumors at the age of 10 months.

They injected six 2-month old cancer-prone mice with a vaccine that contained the α-lactalbumin antigen and an adjuvant (a chemical that boosts the immune system to help the vaccine), and another six had a dummy injection that did not contain the antigen. None of the mice had cancer when they were injected.

After 10 months, all the mice that had not received the antigen had developed large breast tumors, while none of the mice that had received the antigen showed signs of breast tumors.

The authors wrote also that "vaccination-induced prophylaxis occurs without any detectable inflammation in normal nonlactating breast tissue", and concluded:

"Thus, α-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."

The researchers also found that the vaccine inhibited tumor growth when injected in mice that already had breast cancer tumors.

There are already two cancer-prevention vaccines approved for use in the US, one against cervical cancer and the other against liver cancer, but these target viruses, the human papillomavirus (HPV) and the Hepatitis B virus (HBV), and not the cancer itself.

Dr Joseph Crowe, Director of the Breast Center at Cleveland Clinic, said because Tuohy was an immunologist rather than a cancer specialist he approached the problem from a different angle: attack the tumor itself.

"It's a simple concept, yet one that has not been explored until now," said Crowe.

Tuohy said he thinks their findings go beyond breast cancer, and give us a glimpse of how we might develop vaccines against other types of cancer.

For instance, in line with these findings, scientists could search for antigens for other cancers; they would have to meet the same criteria, which are: must be over-expressed in the majority of targeted tumors and must not be present in normal tissue, except under specific avoidable conditions (such as lactation).