Peripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A).
Reverse transcription-polymerase chain reaction (RT-PCR) analysis for interleukin 4 receptor alpha (IL-4Ralpha), interleukin 13 receptor alpha1 (IL-13Ralpha1), interleukin 2 receptor gammac (IL-2Rgammac) were performed on total RNA extracted from 10 non-invasive pituitary adenomas, 30 invasive pituitary adenomas, one glioblastoma multiforme, one normal human pituitary tissue sample and one normal human brain tissue sample.
Glioblastoma cell lines transduced with this vector could produce high levels of IL-2 for up to 2 weeks, long enough to elicit an antitumor immune response.
Four patients affected by glioblastoma recurrence were treated with a gene therapy-immunotherapy protocol consisting of intratumoral injections of culture cells producing a retroviral vector which expresses human interleukin-2 and the herpes simplex virus thymidine kinase genes.
T cell suppressor factor produced by human glioblastoma cells inhibits T cell proliferation in vitro and more specifically interferes with interleukin-2 (IL-2)-dependent T cell growth.