What Types of Immunotherapy Treat Osteosarcoma?

Immunotherapy vs. Chemotherapy

Chemotherapy — a key feature of the standard treatment for osteosarcoma — uses powerful drugs to attack abnormal cells throughout the body, but the treatment comes with numerous downsides. Chemotherapy does not distinguish between cancer cells and healthy cells, resulting in toxicity and severe side effects for the patient, including nausea, vomiting, hair loss, weight loss, and fatigue. In addition, some osteosarcomas do not respond to chemotherapy, and chemotherapy can miss microscopic tumor cells that then go on to cause a relapse.

Immunotherapy is relatively new, with the first immune checkpoint inhibitor approved by the FDA in 2011. Immunotherapy drugs strengthen or train the immune system to better fight off cancer cells. Immunotherapy tends to be much better tolerated than chemotherapy, causing fewer and less-severe side effects.

What Types of Immunotherapies Are Available?

Robbie Majzner, MD

Immunotherapy has generated a lot of attention in the past decade, and for good reason. It is very effective at treating certain cancers. One type of immunotherapy uses T cells, a type of white blood cell, to target and kill cancer cells.

“Immunotherapy works really well in certain adult cancers like melanoma and lung cancer,” says Robbie Majzner, MD, director of the Pediatric and Young Adult Cancer Cell Therapy Program at Dana-Farber Cancer Institute/Boston Children’s Hospital. “It works because T cells respond to mutations.”

Katy Rezvani, MD, PhD

But osteosarcoma and other pediatric cancers do not have as many gene mutations as adult cancers, so they are much harder for the immune system to locate. They also are notoriously difficult for immune system cells to penetrate and survive in.

“The physical barrier of the cancer prevents the immune system cells from entering,” says Katy Rezvani, MD, PhD, section chief of cellular therapy at The University of Texas MD Anderson Cancer Center. “Then, even when the immune system cells get in, the microenvironment is so toxic that it has really made the whole process very challenging.”

There has been little success so far in developing immunotherapy that is effective against osteosarcoma, which is why research is so important.

What Types of Immunotherapies Are Being Studied?

Researchers are learning more about osteosarcoma and the immune system all the time, and that knowledge is being applied to the development of immunotherapies for osteosarcoma. Two especially promising areas of study are CAR T cell therapy and natural killer cell therapy.

CAR T Cell Therapy

On their own, T cells are not very good at locating certain cancer cells. To mitigate this, researchers have devised a way to outfit T cells with a sort of geolocation system. By adding a chimeric antigen receptor (CAR) to T cells, these cells are better able to seek out camouflaged cancer cells.

CAR T cell therapy is being explored with some first signs of efficacy for the treatment of neuroblastoma, another predominantly pediatric cancer that shares some genetic properties with osteosarcoma. A phase I trial testing the effectiveness of CAR T cell therapy in osteosarcoma and neuroblastoma is open at ten centers around the country.

The more that CAR T cells can distinguish osteosarcoma cells from normal cells, the more effective this therapy becomes. That is why Dr. Majzner’s lab is dedicated to understanding what is on the surface of osteosarcoma cells with the intent of identifying targets for the immunotherapy to seek out.

“We are trying to make more complex systems for recognizing cancer versus normal tissue,” Dr. Majzner says. “My lab recently invented a technology that could make the T cell only fire when you have two targets. This would prevent the T cell from attacking, say, bone or healthy lung cells and instead attack only osteosarcoma cells.”

Natural Killer Cell Therapy

Dr. Rezvani’s lab is focused on using a different immune system cell, the natural killer (NK) cell, to fight osteosarcoma.

“Natural killer cells are some of the most effective immune system cells that we have in our body,” she says. “They are very good at killing cancer cells, and actually, they are very good at killing osteosarcoma cells.”

There are benefits to using NK cells versus CAR T cells.

“With NK cells, we do not have to rely on using the patient’s own cells, which do not function as well after having been through rounds of chemotherapy,” Dr. Rezvani says. “We also do not have to worry about any potential for the patient developing graft versus host disease, which can occur when T cells from a donor are used.”

As such, Dr. Rezvani’s immunotherapy uses NK cells from umbilical cord blood that would otherwise have been discarded. This method allows the therapy to be produced ahead of time, saving patients from having to wait for their blood to be collected, sent to a lab for a CAR T product to be manufactured, and then infused — a process that typically takes about two weeks.

But developing an immunotherapy treatment that uses NK cells has its own challenges, namely identifying cancer cells. So Dr. Rezvani’s lab has devised a way to outfit NK cells with CARs, just like in CAR T cell therapy.

Following a successful pilot study, MD Anderson is now accepting osteosarcoma patients who have treatment-resistant or relapsed disease to participate in Dr. Rezvani’s research.

Dr. Rezvani’s lab at the University of Texas MD Anderson Cancer Center

When Will These Therapies Be Available?

While immunotherapy for osteosarcoma looks promising, research, drug development, testing, and manufacturing all take time. Both Dr. Rezvani and Dr. Majzner say we are likely still years away from immunotherapy being widely available to osteosarcoma patients.

The OSI is helping accelerate progress by sponsoring several immunotherapy research projects as part of its research portfolio.

“It is difficult to say exactly how long, but I hope people know we are pushing through as fast as we safely can,” Dr. Rezvani says. “We know novel therapies are urgently needed by patients with osteosarcoma, and we feel that sense of urgency.”