Abstract 2758: Expanding PRISM high-throughput screening capabilities to other modalities

Abstract

Abstract PRISM, a high-throughput drug screening platform, has been used extensively to profile DMSO-soluble compounds, including nearly all commercially available FDA-approved small molecule drugs, in pools of cancer cell lines. In addition to these highly-optimized compounds, novel small-molecule libraries comprising tens of thousands of compounds have been screened through collaborative partnerships. While PRISM has been highly effective in discovering new therapeutic targets and classes via libraries of this nature, we have not yet explored screening aqueous molecules at scale, such as antibodies, antibody-drug conjugates (ADCs), cytokines, and other biologics. There is also untapped potential for the further development of PRISM-based assays utilizing more physiologically relevant assay conditions to gain new insights into cancer biology and highlight more clinically relevant targets. Specifically, the incorporation of environmental cues such as media nutrients, extracellular matrix, and other non-cancer cell types can have a drastic impact on cancer cell state, and thus cancer cell responses to therapy. For example, PRISM pools grown as 3D spheroids, compared to 2D mono-layers, reveal models showing increased sensitivity to mutant KRAS inhibition. Similarly, the addition of immune effector cells, via co-culture methods, to the PRISM platform will enable identification of key mechanisms involved in antibody-dependent cellular cytotoxicity and measurement of immunotherapeutic-relevant phenotypes at an unprecedented scale. This coupling of aqueous screening, with the addition of relevant tumor-microenvironmental cues may help identify therapies more destined to succeed in the clinic, and delineate novel mechanisms involved in cancer cell-state that underpin the many clinical challenges we face in curing cancer. Citation Format: Jacob Smigiel, Jillian Eskra, Antonella Masciotti, Aydin Golabi, Blanche Ip, Melissa Ronan, Matthew G. Rees, Jennifer Roth. Expanding PRISM high-throughput screening capabilities to other modalities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2758.