Vaccination with autologous, non-attenuated, live glioblastoma cells induces potent peripheral and intratumoral anti-tumoral responses - a First In Human experience
Ilan Volovitz1*, Nati Shapira1, Irun R. Cohen2 , Lea Eisenbach2, Rachel Grossman1 and Zvi Ram1
1Cancer Immunotherapy Lab, Dept. of Neurosurgery, Tel-Aviv Medical Center, Tel-Aviv, Israel; 2Dept. of Immunology, Weizmann Institute of Science, Rehovot, Israel
* Corresponding author
Glioblastoma (GBM), which grows uninhibited in the brain, almost never metastasizes outside the brain. The rare occurrence (<0.5%) of overt GBM extracranial metastasis are paradoxically associated significantly enhanced survival.
We previously reported that the highly malignant F98 Fischer-rat GBM, which grows aggressively in the brain, spontaneously regresses when injected as live unattenuated cells subcutane. The peripheral growth and regression of live glioma cells markedly enhanced the survival, or cured rats challenged with the same tumor cells intracranially. The difference in response to glioma cells inoculated in peripheral versus intracranial sites was shown to be immune mediated, and was termed ‘Split immunity’.
We now report the results of two GBM patients treated in a First in Human (FIH) trial using the Split Immunity concept. The patients were vaccinated subcutane with autologous irradiated tumor cells and then with live non-attenuated cells.
The treatment caused no serious adverse events. Live tumor cells neither grew at the injection site nor did they metastatically spread. Elaborate multicolor flow cytometric tools detected potent anti-tumoral polyfunctional activation in 2.5%-5% of peripheral CTL and Th, respectively, following live-cell vaccination. Full intratumoral immune mapping exhibited major changes (x8-x200) following treatment, in the frequency of plasmacytoid and myeloid DC (CD141+ and CD1c+) which also upregulated their maturation markers. Other intratumoral cells exhibiting major increases were CD56Brt NK cells in one patient, and Th and CTL in the second patient.
The accumulated FIH results are suggestive of safety and efficacy and will soon be pursued in a phase IIa clinical trial.