Structural and functional characterization of integrin α5-targeting antibodies for anti-angiogenic therapy.

Integrins are a large family of heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1, also known as the fibronectin receptor, is a key mediator of angiogenesis and its dysregulation is associated with tumor proliferation, progression, and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful in large part due to efficacy and off-target effects.

Key role of a structural water molecule for the specificity of 14F7-An antitumor antibody targeting the NeuGc GM3 ganglioside.

Tumor-associated glycolipids such as NeuGc GM3 are auspicious molecular targets in antineoplastic therapies and vaccine strategies. 14F7 is a monoclonal IgG1 with high clinical potential in cancer immunotherapy as it displays extraordinary specificity for NeuGc GM3, while it does not recognize the very similar, ubiquitous NeuAc GM3. Here we present the 2.

Crystal structure of an L chain optimised 14F7 anti-ganglioside Fv suggests a unique tumour-specificity through an unusual H-chain CDR3 architecture.

Targeted cancer immunotherapy offers increased efficacy concomitantly with reduced side effects. One antibody with promising clinical potential is 14F7, which specifically recognises the NeuGc GM3 ganglioside. This antigen is found in the plasma membrane of a range of tumours, but is essentially absent from healthy human cells.