Evidence shows new Temferon may have activity in glioblastoma

Early results from the Phase 1/2a TEM-GBM study presented at the 2022 AACR Annual Meeting showed that temferon may affect the tumor microenvironment in glioblastoma.

Immune system activation and tumor microenvironment alteration were observed effects in glioblastoma patients treated with temferon, a genetically modified monocyte expressing Tie2 (TEM) targeting interferon-α2 (IFNα2), according to early results of the TEM-GBM phase 1/2a study (NCT03866109) presented in a poster at American Association for Cancer Research (AACR) 2022 Annual Meeting.

“These results provide initial evidence for the targeted activity of Temferon in GBM,” said Bernard Gentner, MD, study co-author and head of the Stem Cell and Leukemia Translational Research Unit at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

Temferon is an experimental advanced therapy consisting of CD34+-enriched autologous hematopoietic stem and progenitor cells exposed to transduction with a lentiviral vector, resulting in the expression of myeloid-specific IFNα2. Gene-modified TEMs target IFNα2 expression in the GBM tumor microenvironment.

“To ensure stable delivery of genetically modified TEMs into the tumor, we transduce hematopoietic stem and progenitor cells with a lentiviral vector carrying the IFNa2 transgene transcriptionally regulated by the Tie2 promoter and by post-transcriptional elements that ensure that the transgene is expressed only in myeloid cells that are recruited to the tumor,” Gentner said.

TEM-GBM is an open-label, dose-escalation study evaluating the safety and efficacy of Temferon in up to 21 newly diagnosed patients with GBM harboring an unmethylated MGMT promoter. After surgical resection, up to 15 patients received 1 of 3 increasing doses of Temferon and 1 of 2 different conditioning regimens in Part A of the trial. In Part B, another 6 patients will receive a single dose of Temferon at the recommended Phase 2 dose.

After completion of radiation therapy, patients received a conditioning regimen of carmustine (BCNU) and thiotepa (Tepadina) in Cohorts 1–4 or busulfan (Busulfex) and thiotepa in Cohort 5 prior to administration. from Temferon.

Monitoring of hospitalized patients takes place until hematological recovery, then patients will be followed regularly for up to 720 days. At this point, patients are asked to participate in a long-term follow-up study for an additional 6 years.

Eligible adults between the ages of 18 and 70 must have an ECOG performance score of 0 to 1, a Karnofsky performance score greater than 70%, and adequate heart, kidney, liver, and lung function. Patients with active autoimmune disease or who received oral or parenteral chemotherapy or immunotherapy within 2 years of screening are excluded.

The primary endpoints of the study are Temferon engraftment within the first 90 days, the proportion of patients achieving hematological recovery 30 days after autologous stem cell transplantation, and the short-term tolerability of Temferon as as defined by a stable blood count, absence of cytopenias, absence of significant organ toxicities above grade 2, and absence of replication-competent lentivirus.

As of October 15, 2021, the data cut-off date, the median follow-up was 267 days (range: 60-749). Patients in cohorts 1 to 3 received a dose of 0.5 to 2.0 x 106/kg Temferon with an average vector copy number of 0.70 and a transduction efficiency of 54%. Those in Cohorts 4 and 5 received 2.0 x 106/kg Temferon with an average vector copy number of 0.77 and a transduction efficiency of 49%.

Investigators observed increasing proportions of differentiated Temferon-derived cells, as determined by the presence of vector genomes in peripheral blood and bone marrow cell DNA, reaching up to 30% at 1 month in the treatment cohort highest (2.0 x 106/kg). These differentiated cells persisted at lower levels for up to 18 months.

“All the patients showed live Temferon transplant,” Gentner said. “Graft take was highest at 1 month and in many patients was around the entry fraction. …Graft take then declined, stabilizing at 3-6 months around 10% .

“Despite the large proportion of modified cells, only very low to moderate concentrations of interferon alpha were detected in plasma and cerebrospinal fluid, indicating tight regulation of vector expression.”

Gentner added that Temferon did not delay hematopoietic recovery and the neutrophil and platelet transplant was similar to the standard autologous stem cell procedure.

Investigators did not detect any dose-limiting toxicity. Gentner said adverse events so far have been related to progression or the transplant procedure, not IFNα2 itself.


Gentner B, Finocchiaro G, Farina F, et al. Genetically Engineered Tie-2 Expressing Monocytes Target IFN-α2 in the Glioblastoma Tumor Microenvironment (TME): Preliminary Data from the TEM-GBM Phase 1/2a Study. Poster presented at the 2022 AACR Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract 5213.

Irene B. Bowles