Medicine is making big gains in the battle against cancer, enlisting the body’s own immune system to control or eliminate previously deadly tumors with a host of new treatments.
Immunotherapy using drugs called PD-1 and PD-L1 inhibitors have dramatically increased survival times for some deadly cancers, including melanoma and certain lung, bladder, and kidney carcinomas. These drugs don’t kill cancer cells; instead, they make it harder for them to hide from the body’s cancer-killing T-cells.
Now, personalized cancer vaccines are further transforming the battlefield. They use genetic sequencing to identify specific mutations in a person’s cancer and, like the Covid vaccines that use the same approach, spur his or her immune system to crank out T-cells targeting cancerous cells with that mutation. The personalized vaccines mostly are available only in drug trials at the moment, but some should be hitting the market in the next few years.
In 2022, President Biden set a goal of reducing cancer deaths by at least 50% over 25 years. Cancer is expected to kill about 610,000 Americans this year, according to the National Cancer Institute. Oncologist James Gulley, co-director of the institute’s center for Immuno-Oncology tells Barron’s there is a good chance that Biden’s goal will be met with the new treatments.
“In the last 10 to 15 years…the addition of effective immunotherapy has really changed how we treat multiple cancers,” he says.
How These Treatments Work
To understand how immunotherapy works, you first have to understand how the body’s immune system naturally battles cancer. Every cancer begins with a mutation. Your own T-cells are programmed to recognize cells that are foreign to the body and kill them.
The problem is that cancers have evolved their own mechanisms for turning off T-cell activity. The PD-1 and PD-L1 inhibitors rev up the T-cells, and enable them to begin destroying cancerous cells again.
That may not be enough. Sometimes the body won’t mount a significant immune response until the cancer has gotten so advanced it’s a losing battle.
That’s where cancer vaccines come in. They help the body boost production of the right T-cells to target particular cancers before they get out of control.
“If you look over the last 20 years, we’ve really evolved from thinking about cancer as anatomical—breast, prostate, etc.—to hundreds of individual cancers that are really based on the specific biology of the tumor itself,” says William Dahut, chief scientific officer for the American Cancer Society.
Where Treatments Are in Pipelines
The National Cancer Institute’s Gulley points to the advances in treating melanoma, the most deadly skin cancer, as an example of the potential for these drugs. In a recent trial, a PD-1 inhibitor from
Merck
in combination with personalized cancer vaccines developed with
Moderna
were given to patients after they had surgery to remove their melanoma. Melanoma often returns after that surgery and can be fatal. But the drug-vaccine combination reduced the rate of recurrence or death by 44%, the two companies announced in December.
Merck’s Keytruda was first approved in 2014 and is widely used today by oncologists. Approval of Moderna’s personalized cancer vaccine could take another two to four years, depending upon regulatory concerns, says Kyle Holden, Moderna’s head of development, therapeutics and oncology. While Moderna has only tested the vaccines against melanoma, Holden says he is hopeful the shots eventually can be deployed against many other cancers.
“Every cancer has mutations, so we believe we should be able to create a vaccine for every person who has a cancer,” Holden says. “Whether or not that vaccine works will have to be tested in clinical trials.”
Moderna plans to expand testing to additional tumor types, including non-small cell lung cancer, which kills more Americans than any other cancer.
Oncologist Jedd D. Wolchok, Meyer Director, Sandra and Edward Meyer Cancer Center, says when he began treating patients in 2000, the median survival time for a person with metastatic melanoma was between six and seven months. Now it is six years.
“That’s how an awful cancer can be turned around when the right science becomes ripe for translation into new therapies,” he says. “That clearly hasn’t happened with some other cancers.”
Know the Risks
Part of the reason Moderna and
Pfizer
–
BioNTech
were able to create effective Covid vaccines so quickly is that they used platforms already being studied for cancer vaccines. Moderna’s Holden says that his company largely halted work on its cancer vaccines during the early days of the pandemic to focus on the Covid vaccine.
Moderna’s personalized cancer vaccine has roughly the same side effects as its Covid vaccine, Holden says. Recipients frequently have soreness at the injection site and run a fever for a day or two.
PD-1 and PD-L1 inhibitors have more substantial side effects. By heightening the body’s immunological response, they can produce side effects that cause patients to stop taking the drug or on occasion are life-threatening—such as impaired breathing, the American Cancer Society’s Dahut says. “The immune system is very powerful, and sometimes if you’re unleashing the brakes, it can go in directions you don’t want it to go,” he says.
Wolchok of the Sandra and Edward Meyer Cancer Center echoes this: “People have died from these drugs. No questions about it. It is a constant risk-benefit balance that we go through.
That said, the new immunotherapy drugs are generally far safer than chemotherapy, which was the standard treatment for cancer before immunotherapy arrived.
Chemotherapy continues to be used. But oncologists now are often using it in combination with immunotherapy, and finding that makes chemotherapy more effective.
Doctors Holden and Dahut both worked as clinical oncologists earlier in their careers, when cancer more often was a death sentence “I was in the position where I had to tell people I have no further treatments I can give you,” Holden says. And I don’t want doctors to be in that position. I don’t want patients to be in that position.”
Getting These New Treatments
While huge progress has been made in combating certain cancers like melanoma, survival times have barely budged for others like pancreatic cancer and brain tumors. But if you have cancer or a loved one has certain cancers, the new treatments can be game changers.
Because the battlefield is changing rapidly, you and your oncologist may have to do more work to make sure you are getting cutting-edge treatment. Sometimes, you may have to enroll in trials to get the latest immunotherapy advances. If you’re a cancer patient, this government website has information on ongoing trials. Holden says Moderna will be running new trials on personalized melanoma vaccines in the near future, and that it should appear on the website.
Ask your oncologist to order genetic sequencing on your cancer, says oncologist Dahut of the American Cancer Society. “It’s good advice for all patients with advanced cancer to have sequencing because they may uncover a targeted therapy including immunotherapy,” he says.
Says Dahut: “It is such a different world than back in the 1990s.”
Write to Neal Templin at [email protected]
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