Brain tumor treatment breakthrough! Antibody fusion cytokine clinical trials are under way.

Text . . . In a paper published in Science Translational Medicine on October 7th, a team of researchers from research institutions such as the University Hospital zurich in Switzerland and philogen, an Italian biotechnology company, combined antibodies targeting glioblastoma with cytokines to produce fusion proteins that can be delivered intravenously and accumulate in tumors, and showed high anti-tumor activity in mouse models and in studies in human patients.
Source: Science Translational Medicine glioblastoma is the most invasive primary brain tumor, which has been considered an immunological "desert" because of the difficulty and side effects of surgical removal of tumors, and the highly immunosuppressive tumor microenvirons that make it almost impossible for the drug to work on tumors.
cytokines are the main regulatory factors of the immune system, although they can make "cold" tumors "hot", but unmodited cytokines are too toxic for patients to bear.
it is necessary to use new methods for the selection and engineering of cytokines to ensure their safety and effectiveness.
the study, researchers tested cytokines IL-2, IL-12 and TNF in combination with antibody L19 (L19-IL2, L19-L19-in-a-mouse models of immunological gliomas) Treatment effects of mTNF and L19-mIL12 (previous studies have shown that L19 selectively locates patient primary and secondary brain tumors when intravenously radioactively labeled L19-based antibody coupled).
results showed that the anti-tumor effect of the fusion of the two proteins was more significant than that of using two of them alone.
, the accumulation of L19-IL2 and L19-mTNF in glioblastoma slowed tumor growth and 40% of animals were cured.
180 days after the first treatment, the researchers implanted a second group of tumor cells into the brain hemisphere on the other side of the mouse, and the mice were still protected without further treatment intervention, demonstrating the continuity of the anti-tumor immune response induced by fusion molecules.
trials of fusion proteins showing effective anti-tumor activity in mouse models (Source: Science Translational Medicine) Fusion Protein (NCT03779230) are also under way.
researchers tested the TNF fusion protein (Fibromun) in three patients with glioblastoma.
two of the patients remained stable at 6 months of treatment, and the area of necroticity in the tumor area increased.
this clinical study is currently recruiting more patients.
Fibromun molecules (source: Philogen.com) use L19-TNF to treat patients with relapsed glioblastoma (source: Science Scienceal Medicine) but the team also points to the limitations of this clinical trial: the number of patients is small and patients receive only one dose level of L19-TNF, so further research is needed to fully understand the safety and effectiveness of this treatment.
reference: 1 s Tobias Weiss et al. Immunocytokines are adioedd immunotherapeutic again approachst glioblastoma. Science Translational Medicine (2020) 2 s New immuno-oncology combo attacks glioblastoma in mice and paves path to human trials (Source: Fierce Biotech)