The Practical Dream of Cancer Therapies and Vaccines

By Jason Socrates Bardi

In the field of cancer research, to "cure" is, perchance, to dream.

To dream of helping the masses who are every year treated for cancer or of saving over 500,000 Americans who succumb every year to cancer. But believing in a cure is perhaps to slip into foolhardy fantasies. We may never find a single magic bullet that can successfully cure all types of cancer.

Immunology Professor Ralph Reisfeld freely admits to being a dreamer, although he is also enough of a realist to avoid using the word cure.

"In science you have to dream a little bit," he says. "My dream is to prevent cancer."

"And," he adds "if you can't prevent cancer, then at least you can help doctors treat it better. That would be a real boon for mankind."

Cancer is a quasi disease—actually over a hundred diseases caused by various sorts of mutations inside various cells in various tissues.

These mutations upregulate some genes, increasing the expression of metalloproteases for instance, and downregulate others, shutting off production of receptor proteins. After a certain number of such events occur, a cancer cell grows out of control, becoming what is known as a tumor. Tumors threaten the tissues where they are located. Worse, tumors can metastasize and migrate through the bloodstream to other tissues—the reality of malignant carcinoma that claims so many lives every year.

Immunotherapy—Helping the Body Do What it Should

One approach to cancer therapy that has evolved over the last few decades is the method of immunotherapy, which aims to give the immune system a push to start doing what it should be doing in the first place—killing cancer cells. Immunotherapy involves helping the T lymphocytes and other cells of the immune system attack and kill cancer cells, and it is best at killing small colonies of cancer cells before they grow into tumors.

One way in which this is accomplished is by presenting the immune system with tumor-specific antigen. Antigens are markers—proteins on the surface of a cancer cell, for instance—that are used by the immune system to distinguish one cell from another. Immunotherapy entails administering injections of the antigen and activating the immune system against it.

These injections enable the antigens to be presented by professional antigen presenting cells, which very effectively stimulate the immune system. After recognizing the antigens presented by the antigen presenting cells, the immune cells become activated and mount an immune defense, selectively attacking any other cells displaying the antigens—the cancer cells.

Since cancer cells are originally "self" cells, the trick is to find some antigen that they display, but which normal cells in the body do not. Fortunately, the mutations that cause cancer often cause distinct antigens to appear on the surface of cancer cells. Sometimes these antigens are overexpressed on cancer cells, decorating them much more so than normal cells, and sometimes the antigens are expressed only on cancer cells. But in any case, they mark the cancer cells, and when the immune system is stimulated to specifically attack cells with those antigens, the cancer cells can no longer hide behind their self faŤade.

"[Cancer] cells masquerade as self," says Reisfeld. "We do everything we can to take the mask off."

Reisfeld employs a technique called passive immunotherapy, which involves giving antibodies to a patient that are specific to tumor cell antigens. The antibodies bind to molecules on the surface of tumor cells and direct other, cytotoxic immune cells to them.

One such antibody he discovered is the monoclonal antiganglioside GD2, which is currently in Phase III clinical trials sponsored by the National Institutes of Health. GD2 targets the ganglioside proteins that are expressed on the surface of neuroblastoma tumors, the second leading cause of childhood cancer and one for which there is usually a poor prognosis.

"These children have been dying in far too large numbers," says Reisfeld, statistics that he hopes GD2 will change.

In the therapy, a recombinant protein is given to a patient intravenously. The protein is the antibody that is linked to the cytokine interleukin-2 (IL-2)—a molecule produced by immune cells that is important in cell growth, adhesion, and movement. IL-2 is a growth factor for immune cells, like T cells, macrophages, and natural killer cells. IL-2 binds to receptors on their surfaces, activates them, and helps them proliferate.

So the recombinant protein does four things. By virtue of its GD2 component, it finds the neuroblastoma tumor cells, binds to them, and attracts immune cells that can kill them. And significantly, because of the IL-2 component, the recombinant protein enhances this killing by activating the immune cells and inducing them to multiply at the site of the tumor.

"GD2 is almost like a guided missile to bring interleukin to the tumor," says Reisfeld.

Immunotherapy works best at slowing down metastasis in minimal residual disease, preventing the growth and spread of cancers. It is not designed to kill big, bulky tumors or address widespread metastasis. "There we need the surgeon, the radiologist, and the chemotherapist," says Reisfeld. "They do that."

One patient, he adds, has had great success since starting the treatment at the age of five. "Now he's 16 and a big boy," Reisfeld beams, pointing to a picture on his shelf of a boy, smiling.


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"In science you have to dream a little bit," says Immunology Professor Ralph Reisfeld. "My dream is to prevent cancer." Photo by Jason S. Bardi.