Intratumoral Pressure, Intratumoral Partial Oxygen Pressure, and Inflammatory Cytokines in Antisecretory Factor Treatment of Glioblastoma

Background and Rationale Glioblastoma is the most prevalent primary brain tumor and has the poorest prognosis. Antisecretory factor (AF) is a crucial 41 kDa endogenous protein initially identified for its ability to inhibit experimental diarrhea. The active amino-terminal segment of AF has been synthesized into a 16-amino acid peptide (AF-16) and utilized in animal studies. Salovum®, a product based on the egg yolk powder B221®, contains high levels of AF and is classified as a "food for special medical purposes" by the European Food Safety Agency. It is available over-the-counter in Swedish pharmacies. Specially processed cereals (SPC®) have been shown to induce circulating AF after ingestion.

Many tumors, including glioblastoma, exhibit higher interstitial fluid pressure (IFP) than surrounding tissues, potentially hindering chemotherapy penetration in systemic treatments and possibly increasing excretion during intratumoral treatments.

In head injury models, AF has been effective in reducing elevated intracranial pressure and improving functional outcomes. Similarly, AF has demonstrated a significant reduction in intracranial pressure and increased survival rates in an experimental model of herpes encephalitis. Preliminary results from our studies indicate that treatment with antisecretory factor in patients with severe traumatic head injuries reduces intracranial pressure and improves treatment outcomes. Since Salovum® is not classified as a drug, clinical trials have only required ethics approval.

AF is an endogenous protein, and no antibody formation has been observed when administered to humans. Despite being administered to hundreds of patients, no side effects have been reported. Egg yolk allergy is a contraindication, though no cases of triggered allergies have been documented. In mouse models of malignant brain tumors, AF-16, Salovum® , or SPC® have been shown to lower interstitial fluid pressure and enhance the efficacy of both systemic and intratumoral temozolomide treatment. AF-16 also exhibits immunomodulatory effects on myeloid cells in vitro and on the secretion of immunomodulatory substances from tumor cells. It remains unclear whether AF's effects in tumor models are due to its antisecretory or immunomodulatory properties, or if the former is a result of the latter. Modulation of circulating complement complexes with proteasome units has also been suggested as a potential mechanism.

Details of Trial Diagnostic biopsies will be performed according to clinical routine under general anesthesia, using intraoperative navigation. Subsequently, two intracranial pressure sensors and one microdialysis catheter (for the first five patients) will be inserted through the same burr hole. One pressure sensor and the microdialysis catheter will be placed inside the tumor tissue, and another pressure sensor will be placed outside the tumor tissue. For the next five patients, an oxygen sensor and a microdialysis catheter will be placed inside the tumor tissue, and an oxygen sensor outside the tumor tissue. The catheters will be fixed in a bone-anchored four-lumen bolt.