Programme : Back to Dr Alan Sandercock
Poster
42

High content screening of cell-surface-selected antibodies in a complex 3D tumour cell model

Discussion

Phenotypic screening for novel therapeutics is a well-established discovery platform for small molecules, but in the large-molecule/biologic space most discovery programmes are target-focussed, with relatively few examples of target-agnostic screens. We have established a platform for isolating antibodies/antibody-mimetics against the cell-surface proteomes of intact, disease-relevant cells by phage-display selections. These antibody panels can be expressed in mammalian cells in 96-well format for phenotypic screening.
In collaboration with O-cell-O, we performed a high-content screen on PC-3 cells in a complex 3-D matrix, treated with a mixed panel of antibodies isolated against several different primary tumour cell types. The effects of the antibodies on cell growth morphology were measured, using machine-learning methods to identify a minimal set of phenotypic features that were able to classify the antibody-induced responses. Antibodies that inhibited the invasive phenotype of PC-3 cells were thereby identified for further analysis.
The antibody panel contained a subset of molecules targeting the cell-surface protein CDCP1 (CUB-domain containing protein 1), which had been isolated in phage-selections performed on primary non-small cell lung cancer (NSCLC) cells. CDCP1 has been linked to cancer invasiveness, metastasis and anoikis resistance, and shows promise as a therapeutic antibody target. In our high-content screen, the CDCP1-targetting antibodies did not all behave similarly; instead these molecules divided into two subsets with opposite phenotypic effects on the cells.
This study demonstrates how high-content screens can potentially be used both as a “lead identification” platform and a means to investigate target biology and therapeutic mode-of-action.
Programme
Add to favourites

Hosted By
ELRIG
The European Laboratory Research & Innovation Group Our Vision : To provide outstanding, leading edge knowledge to the life sciences community on an open access basis
Event Logo Find us on Facebook Follow us on Twitter

Get the App
Get this event information on your mobile by
going to the appstore or google play and search for 'elrig'
iPhone App
Android App
www.myeventflo.com/1791
Login
Eventflo Home
copyright ELRIG, eventflo, Labhoo Ltd 2018