Peptidic and non-peptidic αvβ6 integrin-binding molecules have been used in
the clinic for detection and treatment of tumors expressing αvβ6 integrin, because this protein
is expressed in malignant epithelial cells of the oral cavity, pancreas, breast, ovary,
colon and stomach carcinomas but it is not expressed in healthy adult tissue except during
wound healing and inflammation. This review focuses on the landscape of αvβ6 integrinbinding
molecules and their use in cancer treatment and detection, and discusses recent
designs for tumor detection, treatment, and immunotherapy. In the last ten years, several
reviews about the αvβ6 integrin have been published but no one assessed the landscape of
the αvβ6 integrin-binding molecules and their role in cancer detection and treatment.
Firstly, this review describes the role of the αvβ6 integrin in normal tissues, how the expression
of this protein is correlated with cancer severity and its role in cancer development. Taking into account
the potential of αvβ6 integrin-binding molecules in detection and treatment of specific tumors, special
attention is given to several high-affinity αvβ6 integrin-binding peptides used for tumor imaging; particularly,
the αvβ6-binding peptide NAVPNLRGDLQVLAQKVART [A20FMDV2], derived from the foot and mouth
disease virus. This peptide labeled with either 18F, 111In or with 68Ga has been used for PET imaging of αvβ6
integrin-positive tumors. Moreover, αvβ6 integrin-binding peptides have been used for photoacoustic and fluorescence
imaging and could potentially be used in clinical application in cancer diagnosis and intraoperative
imaging of αvβ6-integrin positive tumors. Additionally, non-peptidic αvβ6-binding molecules have been designed
and used in the clinic for the detection and treatment of αvβ6-expressing tumors. Anti-αvβ6 integrin antibodies
are another useful tool for selective identification and treatment of αvβ6 (+) tumors. The utility of
these αvβ6 integrin-binding molecules as a tool for tumor detection and treatment is discussed, considering
specificity, sensitivity and serum stability. Another use of the αvβ6 integrin-binding peptides is to modify the
Ad5 cell tropism for inducing oncolytic activity of αvβ6-integrin positive tumor cells by expressing
A20FMDV2 peptide within the fiber knob protein (Ad5NULL-A20). The newly designed oncolytic
Ad5NULL-A20 virotherapy is promising for local and systemic targeting of αvβ6-overexpressing cancers. Finally,
new evidence has emerged, indicating that chimeric antigen receptor (CAR) containing the αvβ6 integrin-
binding peptide on top of CD28+CD3 endodomain displays a potent therapeutic activity in a diverse
repertoire of solid tumor models.
Optimized Serum Stability and Specificity of an αvβ6 Integrin-Binding Peptide for Tumor Targeting
