Antibodies from immune phage display libraries for regenerative medicine applications and anti-metastasis therapy

We have generated a panel of high affinity scFv antibodies using chicken immune phage display technology that bind to the primary cilium of a quiescent population of lineage - ve CD45 + ve Mesenchymal Stem Cells (MSCs) that reside in human bone marrow. This MSC subset can be readily isolated using Miltenyi MACs systems, expanded rapidly in culture and can differentiate into bone, cartilage and fat tissue, and are therefore of particular interest in regenerative cell therapy. This panel of recombinant antibodies also bind to a small number of CD14 + ve MCSF + ve, RANK + ve CD51/61 + ve pre-osteoclasts circulating in peripheral blood. Both MSCs and Osteoclasts are cellular targets in anti-metastatic therapies, being implicated in cancer metastasis from its primary site (in the case of MSCs) and in colonisation and survival of metastatic cancer cells in the bone marrow (MSCs and Osteoclasts). We have engineering both humanised scFv and chimeric full length chicken/human IgG1 and are testing the stability and specificity of these antibody constructs. We currently aim to produce stable functional antibody for the isolation of MSCs for regenerative cell therapy, and to demonstrate the anti-metastatic potential of humanised antibodies in antibody-dependent cellular cytotoxicity (ADCC) assays.