The fight against cancer has been a slow and rocky one for physicians and patients. But a promising breakthrough, based on mobilizing the body’s immune system to fight tumor cells, has given rise to an entirely new class of active substances and cell therapy.
Optimism has been steadily growing since the U.S. Food and Drug Administration approved a new class of drugs, known as Yervoy, for the treatment of late-stage, metastatic melanoma three years ago.
“Immune therapy is increasingly proving to be a successful treatment option for cancer,” said Dirk Jäger, a Heidelberg oncologist and head of the Clinical Collaboration Unit for Applied Tumor Immunity at the German Cancer Research Center (DKFZ).
There are still many unanswered questions about immune therapy and it comes with certain risks and side effects. Nevertheless, it has rapidly become one of the hottest fields of research. Several major companies have massively increased their involvement in the field over the past two years.
Citigroup analysts estimate the market potential for cancer immune therapies to be well over $35 billion.
Following Yervoy, two other immune therapies manufactured by the American companies Bristol-Myers Squibb (BMS) and Merck & Co. have been approved in recent months in the U.S for use against skin cancer. They will probably hit the European market later this year.
These drugs are currently being tested for use against numerous other forms of cancer, with more than a dozen other substances in clinical development. There are over 1,000 studies of immunotherapeutic approaches underway worldwide.
Pharmaceutical industry executives are almost euphoric in their enthusiasm. Cancer immune therapy has the potential “to revolutionize the treatment of tumor diseases,” said Daniel O’Day, chief operating officer of Roche’s pharmaceuticals division.
It’s no wonder a great deal of commercial hope rests on developments in the field. Citigroup analysts estimate the market potential for cancer immune therapies to be well over $35 billion and predict the drugs will form the basis for about two-thirds of all cancer therapies within a couple of years.
Market research firm EvaluatePharma sees the new oncology treatments generating average growth of about 11 percent, which could double this already muscular sector of the pharmaceutical industry to more than €132.6 billion ($150 billion) by 2020.
The idea of using the immune system to fight against tumor cells is practically as old as cancer research itself. The German researcher and Nobel Prize laureate, Paul Ehrlich, theorized some 100 years ago that cancer ultimately develops when the immune system fails.
Yet a systematic therapy never developed. Up until now, inoculations only worked by preventing potential cancer-causing virus infections, such as the vaccination against the papilloma viruses responsible for cervical cancer.
New immune therapies don’t target the tumor directly, but rather the checkpoint, where they seek to cancel out its braking action.
Recently, however, scientists have been able to better understand the steering mechanisms of the immune system. Tumor cells protect themselves against the destructive effect of immune cells using, among other things, a special chemical “stop sign” for leukocytes, the white blood cells.
Pharmaceutical researchers speak metaphorically of checkpoints that cancer cells create, which explains why defense cells are inactive when they migrate into tumor tissue.
This is exactly where the new immune therapies are aiming. They don’t target the tumor directly, but rather the checkpoint, where they seek to cancel out its braking action. The main element is a special class of leukocytes, the so-called “T cells.” They have a regulatory function in the immune system, but also are capable of directly attacking and destroying other cells and microorganisms.
In the 1990s, molecular biologists found a receptor called CTL4 on the surface of T cells that gives out a braking signal when activated by certain molecules. By blocking the receptors, the T cells could be reactivated against cancer. This is the concept that produced the cancer drug Yervoy, the first of the new class of so-called checkpoint inhibitors.
Meanwhile, the industry is working on a series of other approaches to activating T cells. Particularly promising, for example, is a concept for cell therapy in which the T cells are removed and reprogrammed outside the body, then reinjected into the patient.
In several small studies at U.S. universities, a complete regression of cancer was achieved in more than 80 percent of patients treated for acute lymphatic leukemia. Mr. Jäger, the Heidelberg oncologist, estimates more than 50 percent of those patients can be healed with such methods.