An anti-TNF-antibody-cytokine fusion combo with chemotherapy turns inoperable brain tumours hot in mice. A Phase I trial sponsored by Philogen SpA is underway.
Swiss researchers have shrinked one of the most lethal and untreatable types of cancer in mice using a combination treatment that proved safe in five patients with glioblastoma. The results suggest that a combo of the anti-TNF antibody-cytokin fusion L19TNF, an anti-TNF antibody that that selectively localises to cancer neovasculature, plus the alkylating chemotherapy chloroethyl-cyclohexyl-nitrosourea (CCNU) cured the majority of tumour-bearing immunocompetent orthotopic mice , whereas monotherapies only showed limited efficacy. The combination induced tumour DNA damage and necrosis.
In a Phase I trial sponsored by Philogen SpA enrolling five patients with glioblastoma, the treatment was largely safe and well-tolerated, and three out of the five patients showed partial responses and signs of tumour shrinkage. Notably, one patient showed a 98% reduction in tumour size and remained stable after 18 months, eight month longer than usually. However, the researchers headed by Tobias Weiss from University of Zurich caution that their clinical trial is still ongoing and is limited by its very small sample size.
According to experts, these initial results suggest the potential to shift the immunological status of glioblastoma from cold to hot, thereby successfully controlling regrowth of the tumour through the use of immunotherapy. The treatment could be even more effective if combined with therapeutic vaccines or CAR-T cell therapy.