An In-depth Appraisal of Cytokine-induced Killer Cells in Glioblastomas Patients

The aim of this study is to optimize the expansion and manufacturing protocol of CIK cells obtained from patients with glioblastoma (GBM) and to assess their interaction with clinical variables, including the use of concomitant steroid therapy and alkylating chemotherapy. The study addresses multiple hypotheses, each corresponding to a specific aim of the project.

For the manufacturing process optimization, the primary hypothesis is that adding hemoderivatives (such as commercial human serum or platelet-derived lysate) can enhance the efficiency of Cytokine-Induced Killer (CIK) cell production (primary endpoint: higher fold expansion) and improve the quality of the final cell product (secondary endpoint: higher CIK viability and anticancer activity). This hypothesis is supported by published data but has not been tested on CIK cells expanded from GBM patients.

The second aim of the study is to evaluate the potential adverse effects of commonly used neuro-oncology therapies on CIK cells. Specifically, the investigators hypothesize that steroids, like dexamethasone, may have a detrimental effect by exerting cytotoxicity and reducing the anticancer activity of CIK cells. Although this hypothesis has been demonstrated for other lymphocyte types, it has not been explored for CIK cells. Establishing potential thresholds for toxicity (median toxic dose) could provide valuable information beyond neuro-oncology applications, considering the broad use of CIK cells in treating hematologic and solid tumors.

Additionally, the study will examine the potential negative impact of temozolomide on CIK therapy. Temozolomide, an alkylating agent, has shown differential cytotoxicity for lymphocytes, with T cells being more sensitive than Natural Killer (NK) cells. The hypothesis here is that CIK cells may inherit the sensitivity to temozolomide from their CD3+ T cell origins. This is particularly relevant, as a recent multicenter Phase III clinical trial evaluating CIK therapy in GBM scheduled CIK cell infusions to coincide with the adjuvant phase of the standard regimen, which involves a higher dosage of temozolomide.

The second part of the study will focus on exploring the immune escape mechanisms employed by GBM to evade Human Leukocyte Antigen (HLA)-independent immunosurveillance, like that mediated by CIK cells.