Engineered vascular-targeting antibody-interferon-gamma fusion protein for cancer therapy

Area of Science:

• Biotechnology
• Oncology
• Immunotherapy

Background:

• Cytokines are potent biopharmaceuticals but suffer from poor tumor localization and severe side effects.
• Targeted delivery of cytokines to solid tumors can improve their therapeutic index.

Purpose of the Study:

• To engineer a fusion protein for targeted delivery of interferon-gamma to solid tumors.
• To evaluate the antitumor efficacy of the engineered fusion protein in preclinical models.

Main Methods:

• Engineered a fusion protein combining an antibody fragment (scFv(L19)) targeting the fibronectin EDB domain with murine interferon-gamma.
• Assessed the fusion protein's tumor targeting and antitumor activity in various murine tumor models.
• Investigated combination therapies with doxorubicin and other immunocytokines.

Main Results:

• The scFv(L19)-interferon-gamma fusion protein successfully targeted tumor neovasculature.
• Significant antitumor effects were observed in F9 teratocarcinomas.
• Efficacy was limited as a single agent in C51 and CT26 tumors but enhanced when combined with doxorubicin.

Conclusions:

• Engineered cytokine fusion proteins can target solid tumors, with efficacy dependent on tumor type and combination therapy.
• The fibronectin EDB domain serves as a viable target for cancer therapy.
• Combination strategies hold promise for enhancing the therapeutic potential of targeted immunocytokines.