On November 9, 2022 Ginkgo Bioworks (NYSE: DNA), the leading horizontal platform for cell programming, reported that it will be presenting a poster on November 11 at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Ginkgo Bioworks, NOV 9, 2022, View Source [SID1234623597]). The poster highlights Foundry-enabled methods for large-scale, combinatorial library design and screening of Chimeric Antigen Receptor (CAR) domains for improved persistence. The ability to screen hundreds of thousands of CAR designs in primary human T cells can enable discovery of variants with desired characteristics. This capability has the potential to discover CAR-T therapies that are effective against solid tumors.
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CAR-T cell therapies show tremendous promise for the treatment of cancer. However, their use to date has been limited to targeting blood cancers, as CAR-T has failed to show consistent efficacy in treating solid tumors, which represent approximately 90% of adult human cancers. Part of the challenge when applying CAR-T therapies to solid tumors lies in T cell exhaustion, a state of dysfunction arising from excessive antigen stimulation in the immunosuppressive environment of a solid tumor.
Signaling cascades triggered by intracellular domains (ICDs) of CARs drive T cell behaviors that correspond to different therapeutic outcomes, including CAR-T persistence. Systematic design and testing of novel ICD combinations that drive more favorable T cell phenotypes has been onerous due to technical constraints in high throughput screening. Data presented at SITC (Free SITC Whitepaper) will demonstrate that Ginkgo’s high throughput screening method enables massively parallel testing of CAR designs, and has led to discovery of new ICD combinations that outperform the canonical CD28-CD3z and 4-1BB-CD3z combinations.
Ginkgo’s platform for cell programming enables synthesis and screening of diverse libraries of genetic constructs to explore biological space. Applying these capabilities to the design of CARs enables screening of hundreds of thousands of possible combinatorial variants of different CAR ICDs. Data presented at SITC (Free SITC Whitepaper) will show how this method could be used to screen for variants with increased persistence in a serial tumor rechallenge assay. As an enabling platform company, Ginkgo can leverage its full stack of mammalian cell engineering expertise and capabilities to enable the high throughput screening of CAR-T cells to discover and optimize future next generation therapeutic candidates for its partners.
"While innovation in CAR-T cell therapies continues to grow at a dramatic pace, CAR-T is still a relatively new modality whose potential is just beginning to be fully explored," said Shawdee Eshghi, Senior Director, Mammalian Engineering, Ginkgo Bioworks. "With large scale screening and automation, Ginkgo has created a tool we believe can dramatically expand the variety and functionality of CAR domains so that our partners can build therapies targeted for particular tumor environments."
"We’ve only seen a small sliver of what revolutionary modalities like CAR-T can achieve in terms of patient outcomes. Being able to explore broader design space for this powerful technology can help unlock new potential in solid tumor treatment, inflammatory and autoimmune diseases, and beyond." said Arie Belldegrun, Executive Chairman and Co-Founder of Allogene Therapeutics and Kite Therapeutics and member of the Board of Directors for Ginkgo Bioworks. "The scale of Ginkgo’s platform helps to enable discovery and innovation in this important arena."
To view the poster, please visit Ginkgo’s blog. To learn more about SITC (Free SITC Whitepaper), to register, or to attend the poster presentation, visit www.sitcancer.org/2022.