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How Much is an Ounce of Prevention Worth?

Reisfeld is also working on DNA vaccines as a possible way to prevent cancer.

The idea of the DNA vaccines is similar to that of immunotherapy. DNA encoding some antigen that will induce a cell-mediated immune response in which T cells are activated to kill cancer cells is injected into a patient so that the antigen can stimulate the immune system. The difficulty, again, lies in finding antigenic components of cancer that are not also present in normal cells, because the cytotoxic T cells will kill whatever they encounter that displays the antigen.

"T cells are mass murderers," says Reisfeld. "Once they begin to kill, they will continue killing."

One promising antigen is a protein called carcinoembryonic antigen (CEA) that appears in early development and soon disappears. In certain cancers, particularly on colon, lung, breast, and pancreatic cancer tissues, this protein is upregulated, though, and reappears specifically on them.

In studies conducted in Reisfeld's laboratory, DNA encoding the CEA antigen is inserted into replication-deficient Samonella typhimurium bacteria and then used in murine model systems. These bacteria are important because they direct the DNA to lymph nodes in the gut—the Peyer's patches where the bacteria die and release the DNA to be taken up by phagocytes, such as antigen-presenting dendritic cells and macrophages. The DNA is translated into protein which is digested in the proteasome of these cells and then presented to T-cells, as complexes with major histocompatibility antigens.

Once the dendritic cells present the antigen to selected T cells, the T cells are activated and proliferate. The T cells will then circulate throughout the body looking for that antigen, and when they encounter it on the surface of tumor cells, they will kill these cells.

The drawback of this approach is that if the antigens happen to be downregulated on the tumor cells, as they often are, then the tumors will be invisible to the passing killer T cells. One possible solution to this is to use the antibody/IL-2 in conjunction with the vaccine to further enhance the ability of the T cells to find the tumor cells. With the IL-2, any T cells that do manage to find some hidden tumor cells will receive the growth signal and expand further.

Reisfeld has tried this, and in some settings has been able to prevent the establishment of metastasis. "We're [now] trying to do this as effectively and as efficiently as we can," he says.

And, he adds, it is entirely possible that in this age of genomics new antigenic targets that are specific to tumor cells will be found in the next few years, which will lead to further possibilities.

"The real excitement is yet to come," he says.


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"The real excitement is yet to come,"

—Ralph Reisfeld