A few good reasons to use nanobodies for cancer treatment

mAbs have been instrumental for targeted cancer therapies. However, their relatively large size and physicochemical properties result in a heterogenous distribution in the tumor microenvironment, usually restricted to the first cell layers surrounding blood vessels, and a limited ability to penetrat...

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Bibliographic Details
Published in:European journal of immunology 2023-09, Vol.53 (9), p.e2250024-e2250024
Main Authors: Jumapili, Neema Ahishakiye, Zivalj, Maida, Barthelmess, Romina Mora, Raes, Geert, De Groof, Timo W M, Devoogdt, Nick, Stijlemans, Benoît, Vincke, Cécile, Van Ginderachter, Jo A
Format: Article
Language:English
Subjects:
Blood vessels
Brain cancer
Brain tumors
Cancer therapies
Nanobodies
Neuroimaging
Physicochemical properties
Tumor microenvironment
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Summary:mAbs have been instrumental for targeted cancer therapies. However, their relatively large size and physicochemical properties result in a heterogenous distribution in the tumor microenvironment, usually restricted to the first cell layers surrounding blood vessels, and a limited ability to penetrate the brain. Nanobodies are tenfold smaller, resulting in a deeper tumor penetration and the ability to reach cells in poorly perfused tumor areas. Nanobodies are rapidly cleared from the circulation, which generates a fast target-to-background contrast that is ideally suited for molecular imaging purposes but may be less optimal for therapy. To circumvent this problem, nanobodies have been formatted to noncovalently bind albumin, increasing their serum half-life without majorly increasing their size. Finally, nanobodies have shown superior qualities to infiltrate brain tumors as compared to mAbs. In this review, we discuss why these features make nanobodies prime candidates for targeted therapy of cancer.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.202250024