By Bill Thomas | September 3, 2024
Immunotherapy is one of the most promising emerging trends in childhood cancer research today. More and more studies seek to explore the potential for immunotherapy to bolster patients’ natural immune responses to better target tumor cells, to the point where, just last year, a New York Times op-ed referred to immunotherapy as a “revolution in cancer treatment”.
Like all scientific revolutions, however, developing safe and effective immunotherapy treatment options is an ongoing process. Some pediatric cancers, such as acute myeloid leukemia (AML), pose unique challenges that make them more resistant to immunotherapy than others.
In addition to being the second most common form of leukemia in children, AML is also one of the most aggressive childhood cancers, with a mere 55-70% five-year survival rate according to the National Cancer Institute. The need for treatment options capable of improving AML patient outcomes is high, yet immunotherapy has thus far proven largely ineffective.
Fortunately, a new paper published in the journal Blood Advances could help change that. Submitted by researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME), the paper details a novel approach to developing a generalized cancer vaccine. This, in turn, could help increase the effectiveness of immunotherapy for AML and other blood cancers.
“We are trying to come up with cancer vaccine approaches that could be more easily scaled and applied,” Prof. Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering at PME, said in a UChicago blog post. “In other words, one type of vaccine that works with a number of cancers.”
The Challenges of AML Vaccine Development
The human immune system is designed to protect us against harmful, abnormal changes in our biology. These changes include the kinds of mutations that cause most cancers. Nevertheless, our immune system sometimes has difficulty distinguishing tumor cells from healthy cells.
“The most common reason why our immune system doesn’t recognize cancer is because cancer cells are smart and they figure out a way to evade the immune system, i.e., tumor-killing cells,” Dr. Kathleen Sakamoto, a professor of pediatric hematology and oncology at Lucile Packard Children’s Hospital, explains. “I’m not sure anyone really understands why this happens for any particular individual. Sometimes it’s because the individual has immune dysregulation or is immunocompromised.”
Dr. Sakamoto’s own work, funded in part by the Pediatric Cancer Research Foundation grants, explores the use of an FDA-approved drug called niclosamide to block the growth of AML tumor cells. Although her work is not directly related to vaccine development, Dr. Sakamoto sees potential in the generalized cancer vaccine approach described in the UChicago research paper.
“There are very few vaccine-type therapies for AML. One of the issues is that the target for the vaccine is also found in normal healthy cells and is toxic. AML cells are heterogeneous and each cell could be different, which makes targeting surface proteins difficult. This results in the ‘escape’ of certain AML cells, leading to relapse,” Dr. Sakamoto says.
“The advantage of personalized cancer vaccines is that they can be tailored to each patient’s leukemia cells. The disadvantage is that this is time-consuming and it’s expensive to have to get them produced and approved for each patient. General cancer vaccines, as suggested in this paper, are certainly appealing.”
A Novel Approach to Immunotherapy for AML
As noted by Dr. Sakamoto, attempts to develop vaccines for pediatric AML have been stymied by the fact that most target antigens found in AML tumor cells are also found in healthy blood cells. This means that any vaccine using these targets runs the risk of harming healthy cells as well as cancer cells.
To get around this, UChicago researchers exploited a unique feature of cancer cells. That is, unlike healthy cells, tumor cells have unpaired cysteine molecules on their surfaces as a result of metabolic and enzymatic dysregulation. Found within the residue of these unpaired cysteines are free thiols, which are highly reactive and capable of interacting with and altering other proteins.
“Our material binds specifically to these free thiols and can covalently link our adjuvant to the tumor cell, tumor debris, whatever the thiol is attached to,” Anna Slezak, one of the paper’s authors, told UChicago’s blog. “This is a way to tag cancer cells or debris of dying cancer cells in the circulating blood for immune recognition and trigger immunity to their mutated proteins.”
To help ensure the vaccine’s efficacy, UChicago researchers combined it with low-dose cytarabine treatments, a type of chemotherapy commonly administered to AML patients. The results? According to the paper published in Blood Advances, the combination of the novel vaccine and cytarabine treatments significantly increased survival rates in individuals diagnosed with AML.
While the researchers acknowledge that more preclinical work is necessary before their novel approach is ready for clinical testing, the fact that the vaccine doesn’t target specific cancer proteins means it may be useful for patients with other blood cancers in addition to AML. Anyone interested in learning more about the team’s research can read the paper published in Blood Advances or the UChicago blog post.
To stay up-to-date with all the latest news shaping the future of pediatric cancer treatment, don’t forget to follow the Pediatric Cancer Research Foundation Profectus Blog!
