Glioblastoma is a devastating brain tumor with no long-term cure. Current therapies rely on surgical resection, high-dose radiation and temozolomide chemotherapy, which significantly decrease patient quality of life and only provide a brief respite from disease. Immunotherapies could present a solution: antibodies and engineered T cells have demonstrated impressive clinical successes for some cancers, but a key challenge in GBM is identification of surface antigens that allow targeting of tumor but not healthy tissues. Notably, cytomegalovirus (CMV) proteins have been observed in >90% of glioblastomas but not healthy adjacent brain tissues, providing a possible means to target novel thera...

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Glioblastoma is a devastating brain tumor with no long-term cure. Current therapies rely on surgical resection, high-dose radiation and temozolomide chemotherapy, which significantly decrease patient quality of life and only provide a brief respite from disease. Immunotherapies could present a solution: antibodies and engineered T cells have demonstrated impressive clinical successes for some cancers, but a key challenge in GBM is identification of surface antigens that allow targeting of tumor but not healthy tissues. Notably, cytomegalovirus (CMV) proteins have been observed in >90% of glioblastomas but not healthy adjacent brain tissues, providing a possible means to target novel therapies to glioblastoma cells. This approach for glioblastoma treatment has been evaluated clinically, using labor-intensive and slow approaches to harvest patient cells and in a lab, train the cells to target the CMV virus before returning the cells to the patients’ body. This approach has increased patient survival, demonstrating the feasibility of targeting GBM via CMV proteins. However, personalized strategies that rely upon growing patient T cells in a lab are necessarily expensive and impose significant time delays in treatment that can be fatal. By contrast, we propose development of antibody-like proteins that target pp65 and recruit immune cells to tumor eradication. This one-size-fits-all therapeutic could be stocked in hospitals and administered to patients shortly after diagnosis. Importantly, protein therapeutics have predictable pharmacokinetics and dosing, low toxicity risks and straightforward manufacturing processes.

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