Integration of Biotherapeutics in Combination Screening with Small Molecule Libraries

Authors

• JS Roth
• L Chen
• J Travers
• CA Klumpp-Thomas
• Z Itkin
• C McKnight
• P Shinn
• R Guha
• Y Fu
• M Ho
• ME Yohe
• DJ Urban
• MD Hall

Abstract

Initiated in 1970s with the onset and development of recombinant DNA technologies, research of biologics as therapeutic agents has been on the rise ever since. In 2017, twelve of the thirty-four FDA approved new entities were biologics, comprised of nine antibodies, one antibody-drug conjugate, and two enzymes. These newly approved therapies are exciting in isolation, but many hold promise for efficacious merging with standard of care regimes to elicit emergent responses. To identify promising cocktails, a systems biology and rational approach can be leveraged, but in the case of novel or poorly understood mechanisms, a high throughput screen of annotated compound libraries can uniquely present tractable synergistic combinations and elucidate underlying biology. NCATS is situated as a premier screening facility with potential to expedite identification of strategic combinations and synergistic mechanisms. However, a minute detail hinders the swift integration of biologics screening –NCATS is solvated in DMSO. Herein we report on the process of incorporating aqueous-solvated biologics into NCATS’ screening platform and present two novel case studies.

Scientific Focus Area: Cancer Biology

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