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Checkpoint Blockade Plus Vaccines Show Synergy in Early GBM Trials

BRIELLE BENYON
Friday, December 06, 2019
Historically, glioblastoma (GBM) is a difficult-to-treat tumor type. Checkpoint inhibition, which has proven successful in multiple other tumor types, has had limited success in patients with GBM to-date—though that could change down the line with the advent of combination therapy, according to recent research presented at the Society for Neuro-Oncology (SNO) annual meeting.

“The early trials of PD-1 inhibition and glioblastoma have had mixed results. By combining something like a standard checkpoint blockade agent with a therapeutic neoantigen vaccine, we're hoping that we can improve the responses we see with these therapies,” said Connor Liu, researcher and medical student at Washington University School of Medicine in St. Louis. “A lot of my work was piloting that combination vaccine plus checkpoint blocking strategy in varying models of glioblastoma.”

Liu spoke with OncLive®, a sister publication of Oncology Nursing News®, about his study examining combination immune treatment of highly aggressive orthotopic murine GBM with checkpoint blockade and multi-valent neoantigen vaccination. The study is the pre-clinical correlate investigating personalized neoantigens in the tumors of patients with recurrent GBM.


OncLive®: Can you give an overview of your study?
Liu: The work I did over the past 2 years really focused on identifying new antigens, tumor-specific mutations in these varying models of glioblastoma. The whole idea is that using a genomic approach to identify these tumor-specific mutations and then to hopefully utilize them in a therapeutic setting, like a cancer vaccine. 

We characterized 2 types of glioblastoma that both have different phenotypes and responses to immune therapies. Then we test these combination treatments in both of those models. 

What is the biggest takeaway? 
Combination immune treatment, at least in these varying glioblastoma models, [can have] some synergistic interaction between these standard checkpoint blockade agents that are already used in a lot of other tumor types but have not been successful in GBM. There's some synergistic interaction with those agents and personalized new antigen vaccine treatments. 

What is the future for treating these patients? 
Especially with something like an aggressive, historically treatment-resistant tumor like glioblastoma, combination modalities definitely [will be the future]. Figuring out how, especially, all these new immune therapy treatments, like checkpoint blockade, adoptive cell transfer, neoantigen vaccines, whatever it may be, and how those treatments interact on a biologic and immunologic level with the current standard of care therapies like surgical resection, temozolomide, chemotherapy, and things like that. 

Understanding that biology is also going to help us tease apart the actual practical aspect of how to treat a patient with glioblastoma, and using all of these agents we have: the timing of it, the dosing of it, the routes of administration. That's where the field is going: understanding how these combination treatments are going to interact together, and how can we best use the options that we have currently to produce the best benefit for our patients. 

What do you think the next steps are? 
For my pre-clinical studies in these mouse models, we see the significance in the combination vaccine and checkpoint blockade, but the question is: why? What is the underlying biology? Are we increasing the number of these tumor-specific effector immune cells in the brain? How is that interacting with these checkpoint blockade agents? That's the next phase of my experiments—understanding the underlying immunology to better optimize the way that we can give these treatments. 





 

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