A preclinical study conducted by a joint team from Switzerland has found that treatment outcomes for glioblastoma patients improved considerably if they received immunotherapy before undergoing surgery to remove the tumors, instead of first having the tumors surgically removed and then receiving immunotherapy.
The study findings appeared in the Nature Communications journal. The researchers are based at UNIGE (University of Geneva) and HUG (Geneva University Hospitals) and were led by Associate Professor Denis Migliorini, who works at UNIGE.
Only a tiny fraction (5%) of glioblastoma patients survive for five or more years even after receiving existing treatments that include surgery, chemotherapy and radiotherapy. The current practice is to surgically remove as much of the brain tumor as possible, and then administer other treatments like chemoradiotherapy and immunotherapy.
The researchers wanted to find out whether there could be a better way to leverage existing treatments in order to improve the clinical outcomes for patients.
The team designed mouse models with glioblastoma and studied the different immune mechanisms at work within the tumor microenvironment before surgery was done and after a surgical procedure to excise the tumor. They noted that the tumor produces TREM2 proteins that suppress the body’s immune system in order to allow the tumor to grow and thrive.
When surgery is done, the resulting wound leads the cancer to go into overdrive in producing TREM2 in order to repair its remaining tissues. As a result, the likelihood of tumor recurrence goes up and subsequent treatments like chemotherapy, radiotherapy or even immunotherapy are less effective because they find the cancer with heightened defense mechanisms that reduce the efficacy of the treatments administered.
The researchers then switched things up and started by administering immunotherapy before surgery to excise the tumor. The immune system of the mice was better able to fight the cancer and brain cancer recurrence was reduced or was delayed.
The team then obtained glioblastoma tumor samples from patients who had undergone surgery and conducted the same tests as had been done in the mouse models. The results were consistent with what they observed in the mouse models, and this suggests that patients could get better outcomes if immunotherapy was given before surgery to remove the tumor.
The researchers plan to conduct a phase 1 clinical trial next year to test the safety of their treatment approach. They will recruit newly diagnosed glioblastoma patients and put them on immunotherapy before surgery is scheduled.
If clinical trials confirm that administering immunotherapy before surgery is conducted meaningfully improves outcomes in larger populations of human subjects, the way brain cancer is treated, or the order in which different lines of treatment are administered could change and make immunotherapy the first line of treatment followed by other interventions like surgery.
This preclinical study is likely to give enterprises like Calidi Biotherapeutics Inc. (NYSE American: CLDI) plenty to think about as they go about their work of developing next-generation immunotherapies targeting different types of cancer.
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