In this project our objectives will be: (i) Production of single chain variable fragments bispecific antibodies targeting KV11.1 channels and adhesion receptors of the integrin family (scDb-Kv_int); (ii) testing the binding and functional activity of the scDb-Kv_int in 2D/3D PDAC cultures, 2D/3D PDAC/PSC co-cultures as well as in 2D/3D cultures from primary human samples; (iii) combining the scDb-Kv_int with pH-sensitive dyes (e.g. SNARF) (scDb-Kv_int_pH) and fine-tuning its affinity to achieve enrichment and maximal activity under the pH conditions of PDAC and to target the PDAC acidic microenvironment; (iv) testing the activity (both imaging and potential therapeutic activity) of the scDb-Kv_int_pH both in vitro (as in (ii)) and in vivo (in xenografted and transgenic KPC mice); (v) linking of the scDb-Kv_int_pH within pH-sensitive chitosan nanogel or produce antibody-drug-conjugate (ADCs) to drive chemotherapeutic drugs to PDAC in vivo. 

(vi) For the set up of the scDb-Kv_int_pH, we will conjugate the single-chain diabody with a NIR (near infra red) fluorescent protein (e.g. miRFPs), which allows a direct monitoring of the protein, without the need of conjugation with other fluorescent moieties; thus facilitating the imaging testing of the antibody.