Frontline Cancer: Retraining your immune system to fight cancer

• FRONTLINE CANCER:

Given the complexities of cancer, there is not – and likely never will be – a single way to destroy it. Instead, the oncologist’s armamentarium must be stocked with many weapons, which include diverse advances in chemotherapy, radiation, surgery and stem cell technologies.

Often, treatment is a combination of the above.

But even combined approaches are not enough. Cancer cells evolve. They fight back. And so, too, must cancer science. Among the most promising developments is immunotherapy, which employs the body’s own immune system to seek out and kill cancer cells and tumors.

“Cancers not only have to figure out how to grow, they also have to learn to evade the immune system,” says Sandip Patel, M.D., a medical oncologist and assistant clinical professor of medicine at UC San Diego Moores Cancer Center. “Our bodies fight foreign invaders such as bacteria and viruses routinely. Our bodies also reject organs from other people, something we actually try to prevent with organ transplants. What if we take that logic and retrain our immune systems to reject a tumor as a ‘foreign organ?’”

Cancer immunotherapy is not a new idea. In the late 1800s, William Coley, a New York surgeon, observed that getting an infection after surgery helped some cancer patients get better. He began injecting patients with certain kinds of bacteria, which came to be known as “Coley toxins,” but his experiments were soon overshadowed by other approaches, such as radiation therapy.

For immunotherapy to successfully emerge demanded a fuller and deeper understanding of how the immune system works and how it can be tweaked to more diligently and smartly attack cancer. That time has come.

Immunotherapy involves different kinds of treatments. Some broadly boost the immune system; others train it to target specific cancer cell types. There are many variations, but I’ll briefly discuss just a few: monoclonal antibodies, cancer vaccines, T-cell therapies and immune checkpoint blockades.

• Monoclonal antibodies (mAbs) are proteins naturally produced in abundant numbers by the body. They circulate through the bloodstream, looking for specific foreign proteins, called antigens, found on invasive microbes and foreign cells. Different antibodies stick to different antigens, and then signal other immune system cells, such as macrophages, to come and destroy the invasive cell.

A lot of research is ongoing to synthesize mAbs specifically designed to seek out proteins found on cancer cells. ‘For example, we’ve just launched the first-ever phase one clinical trial to test a novel stem cell-based mAb therapy for chronic lymphocytic leukemia, the most common form of blood cancer in adults. The approach was discovered and developed here in the lab of Thomas Kipps, M.D., Ph.D., deputy director for research at Moores Cancer Center.

• Some cancers are caused by viruses. Strains of human papilloma virus, for example, have been linked to cervical, anal, throat and other cancers. People with chronic hepatitis B infections are at higher risk of liver cancer. Cancer vaccines work differently than those used against viruses like the flu. Rather than attempting to prevent illness, they are designed to attack a disease that already exists by training the immune system to recognize and attack targeted cancer antigens – and remember them in the future.

• Some treatments stimulate the overall immune system in ways that better help the body rid itself of cancer. They may involve cytokines, such as interleukins and interferons, that help immune system cells grow and divide more quickly. The BCG vaccine, based on a bacterium originally designed to treat tuberculosis, is also used in bladder cancer, where it appears to spur a local immune response against tumors.

• T lymphocytes are a type of white blood cell that play a central role in immunity. Some T cells help other white blood cells. Some destroy foreign cells. Some remain after a threat is eradicated as “memory” against future threats. A variety of immunotherapies focus on different ways to make T cells more effective at their jobs.

Many cancers counter such measures by exploiting the immune system’s safety features for avoid attack on normal cells. These cancers may dim or turn off immune signals to T cells or erect shields behind which they hide or fend off attack. Much progress has been made in stripping away these corrupted protections, knocking down shields so that T cells kill cancer cells.

• This kind of immunotherapy, dubbed checkpoint blockade, has proven very effective for treating melanoma, and researchers at Moores and elsewhere are expanding similar efforts into cancers of the lung, colon, breast, bladder, prostate, kidney, head and neck.

“What if we can release the brakes that have been placed on the immune system by the tumor, so your body's immune system can remember how to fight the cancer and kill it,” said Patel. “This is the current reality of our immunotherapy clinical trials, which look across tumors to the various brakes cancers puts on the immune system. We have therapies that can interfere with those brakes, unleashing the renewed immune system against the tumor.”

Of course, much work remains to be done. Immunotherapy will need to further establish its place in the oncologist’s armamentarium. The ultimate goal, said Patel, is to “teach the immune system to retain memory of how to fight cancer for long-term remission without continuous therapy.”

That requires continued development and perfection of personalized treatments for each and every patient, based upon their particular cancer. Immunotherapy is the ultimate targeted therapy. It is based on the idea that just as every cancer is unique, so too is the remedy that already lies within.

Scott M. Lippman, M.D., is director of UC San Diego Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in the La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman by e-mail: mcc-dir-lippman@ucsd.edu

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