Researchers Use Stem Cells to Produce Cancer-targeting Antibodies

Researchers Use Stem Cells to Produce Cancer-targeting Antibodies

In a new study, researchers have used stem cell proteins to create an antibody that can specifically recognize and be taken up by some types of breast and ovarian cancers.

The study, “Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer,” was published in Scientific Reports.

Antibodies are made by the immune system to fight infections. They work because any given  antibody recognizes one molecular target, called an antigen, with potency and specificity. This quality makes antibodies useful to researchers and clinicians who want to target specific molecules in cells or in patients.

The investigators were hoping to create antibodies that could be used to target cancer proteins, but instead of creating antibodies with cancer cells, they created antibodies with stem cells. Cancer cells and stem cells behave quite similarly, and many antigens are shared between them. These are called oncofetal antigens — literally antigens from early on in development or cancer — and could be useful as cancer targets.

The researchers injected the stem cells in mice and looked for antibodies that targeted these cells. They then tested these on cancer cells and found that one, dubbed A19, could bind and be taken up by a number of cancer cell lines.

Further investigation revealed that A19 specifically binds to the HER2 protein, which is a well-documented molecular target for some kinds of breast and ovarian cancers. Herceptin (trastuzumab, by Genentech), which is used to treat some breast and stomach cancers, also targets this protein, though it targets a different part.

Because A19 was taken up by the cancer cells, the researchers hypothesized they could use that to eliminate the tumors. They created A19 antibodies attached to a cell-killing drug, the rationale being that the antibody could help the drug get into the cancer cell, where it would kill the cell.

The investigators found that these antibody-drug conjugates could effectively kill cancer cells in a dish, and in mice, without any apparent side effects. In fact, treatment with these conjugates reduced the growth of ovarian cancer cells implanted in mice by 60%.

Interestingly, A19 was found to be more specific to HER2 than Herceptin, suggesting it could have a better therapeutic effect. But whether the A19-drug conjugate is better than the Herceptin-drug conjugate, Kadcyla (ado-trastuzumab), remains to be addressed.

“A19 could possibly be developed as an alternative or complementary treatment to Herceptin,” Heng Liang Tan, an author of the study, said in a press release. Further research and clinical trials will be needed before A19 is used in patients, and the researchers hope to continue using their stem cell strategy to create cancer-targeting antibodies.