Pediatric Cancer Vaccine May Be ‘Too Good to Be True,’ But More Work Is Needed

Immune-based therapies have not been as successful in childhood cancer as they have been with adults, but ongoing research is hoping to change that.

Recent years have brought advancements in harboring patients’ immune system to find and fight cancer in adults, but these kinds of immune-based strategies are lagging behind in pediatric patients, said Paul Thomas, a member of the Immunology Department at St. Jude Children’s Research Hospital.

However, ongoing trials are showing that a cancer vaccine may be able to overcome some of the other issues that are present with immune-based cancer treatments like checkpoint inhibition and CAR-T cell therapy, in children.

Finding Targets in Childhood Cancer

Thomas explained that cancer vaccines work by targeting the genetic mutation that is causing the cancer to grow. However, he said that less than 10% of childhood cancers are genetically driven.

“If you've lived a long time, you’ve had a lot of time to accumulate lots of mutations, (and) you might be exposed to certain things that actually cause mutations like pollution, or cigarette smoke or lots of sunlight,” Thomas said in an interview with CURE®. “Whereas kids have been living for less time and so they have fewer mutations in their tumors, and they're often driven by a different kind of mutation than what we see in adult tumors.”

Now, research in pediatric cancer treatment is looking at what kind of mutations or biomarkers can be targeted. For example, he mentioned that one potential target is called the fusion protein, which is when “the body sticks two proteins together that don’t belong together,” according to Thomas.

“The thing we need to look for is figuring out the right formulation of those vaccines and the right way to give them in a way that’s going to overcome the potential immune suppression that tumors exert on the immune system,” Thomas said. “Certain pediatric tumors might be better at that than others, and we really need to come up with clever ways of subverting that signal from the tumor to tell the immune system to calm down.”

The CAR-T Cell Therapy Approach

Additionally, even if pediatric patients do have an immune system against cancer, there is often not big enough of a response to irradicate the tumor, or the quality of response may be lacking.

For that reason, CAR-T cell therapy has been gaining traction, Thomas said.

CAR-T cell therapy, which has become increasingly popular and effective for blood cancer treatment, works by extracting blood from the patient’s body and engineering the T cells (immune cells) to attack cancer. The T cells are multiplied and then infused back into the patient.

“(CAR-T cell therapy) addresses those issues,” Thomas said. “It increases the quantity; you provide a lot of CAR-T cells all at once, and so that problem is overcome. And then you can also modulate the quality as well, you can really read those T cells up and get them ready to go.”

However, this is not a perfect response, either, as tumors — both in children and adults — often find a way to suppress the immune system, which is why trial data has shown that many solid tumors do not respond to treatment with CAR-T cell therapy.

“Solid tumors just create this microenvironment within themselves that we really have to learn more about to effectively target,” Thomas said.

Cancer Vaccines May Be a Better Solution

The cancer vaccine is a third potential treatment option that is being explored for pediatric patients with cancer.

“Vaccines are going to increase the quantity and quality (of immune responses) and it’s going to do so in way that is cheaper and faster and potentially a little less toxic than CAR-T cell therapy,” Thomas said. “So it seems too good to be true… It’s not like it’s the answer for everything yet, but it’s a modality that I think we have a lot of flexibility to try out and change and improve.”

Thomas did explain that the study of pediatric cancer vaccines is still in the early stages, and much of the research to-date has been in CAR-T cell therapy for this population. But as experts continue to learn about the immune system, Thomas remains optimistic.

“What I think we've established as a field in the last 15 years is that the immune system can get rid of every last tumor cell in the body, if we can figure out how to teach it appropriately,” Thomas said. “While we all wish the progress were a lot faster, it is constantly moving every month; there are major advances that make me think we're going to get here sooner rather than later and hopefully, in a way that creates these treatments that are going to be incredibly efficacious, not very toxic and really clearing the deck for a lot of tumors.”


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