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639 Intra-tumor delivery of IFN-alpha by Tie-2 transduced monocytes associated with favorable 2-year survival in unmethylated MGMT GBM patients: preliminary results of TEM-GBM phase 1/2a study
  1. Carlo Russo1,
  2. Bernhard Gentner2,
  3. Marica Eoli3,
  4. Francesca Farina4,
  5. Carlo Russo5,
  6. Elena Anghileri3,
  7. Matteo Barcella2,
  8. Valentina Brambilla6,
  9. Matteo Carrabba4,
  10. Valeria Cuccarini7,
  11. Giorgio D’Alessandris8,
  12. Francesco Di Meco9,
  13. Valeria Ferla4,
  14. Paolo Ferroli9,
  15. Filippo Gagliardi10,
  16. Federico Legnani9,
  17. Stefania Mazzoleni6,
  18. Alessandro Olivi8,
  19. Roberto Pallini8,
  20. Marco Saini9,
  21. Silvia Snider10,
  22. Karen Mullen6,
  23. Luigi Naldini2,
  24. Gaetano Finocchiaro11 and
  25. Fabio Ciceri4
  1. 1Genenta Science, Princeton, NJ, USA
  2. 2San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy
  3. 3Istituto Neurologico Carlo Besta, Milan, Italy
  4. 4Hematology and Bone Marrow Transplant Unit – San Raffaele Hospital, Milan, Italy
  5. 5Genenta Science Spa, Milan, Italy
  6. 6Genenta Science, Milan, Italy
  7. 7Neuroradiology Unit – Istituto Neurologico Carlo Besta, Milan, Italy
  8. 8Neurosurgery Unit – Policlinico Gemelli, Rome, Italy
  9. 9Neurosurgery Unit – Istituto Neurologico Carlo Besta, Milan, Italy
  10. 10San Raffaele Hospital, Milan, Italy
  11. 11IRCCS Ospedale San Raffaele, Milano, Italy
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Glioblastoma multiforme (GBM) is an incurable glial tumor affecting the central nervous system. The reported median survival and the percentage of patient surviving up to 2-years in the unfavorable patients’ subgroup with unmethylated (u)MGMT promoter is 12.7 months and less than then 15% (Stupp et al., 2009), respectively. Despite immunotherapies being able to slow or eradicate numerous tumors, even those metastasized to the brain, none so far have extended survival in GBM.

Methods We have developed a personalized hematopoietic stem cell-based immunotherapy platform delivering immunotherapeutic payloads into the TME through a subset of tumor infiltrating macrophages. Specifically, Temferon has been designed to deliver IFN-α2 within the TME by Tie-2 expressing macrophages (TEMs). Temferon is currently under testing in an open-label, Phase 1/2a dose-escalation study (NCT03866109) evaluating its safety, and biological activity in up to 27 newly diagnosed GBM patients with uMGMT. Temferon is administered by ASCT after the RTx treatment without the concurrent administration of Temozolomide, whose survival benefit is known to be marginal in the uMGMT population.

Results As of June 2023, 4 incremental doses of Temferon (0.5–3.0 x106 cells/kg) have been tested across 21 patients (median age at enrolment 57) assigned to seven cohorts. Median Overall Survival (OS)) after 1st surgery is 15 months (5–40 months). The haematological recovery occurred in all the patients irrespective of dose administered. The percentage of transduced cells found in the BM, reached for the highest dose tested up to the 50% at 1 month and persisted at detectable level in the long-term. Very low median concentrations of IFNα were detected in the plasma, indicating tight regulation of vector expression. Notably, as predicted by TEMs biological behaviour, in the CSF the concentration of IFNa increased concomitantly to evidence of disease progression suggesting increase tumor recruitment of TEMs and subsequent release of IFNa . The 57% of the treated patients underwent a 2nd-line treatment (either pharmacological or surgical) with an interim survival rate at 2-years of 28% (5 of 18 patients; 3 patients excluded as follow-up is below 12 months), which is higher than that reported in literature (15%). One out of the surviving patients was enrolled in a long-term follow-up study and survived up to 3 years after surgery without any 2nd-line therapy added for 2 years.

Conclusions These data provide initial evidence on Temferon potential to counteract disease progression and improve the survival of uMGMT GBM patients.

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