On November 10, 2022 RootPath, a synthetic biology company that elevates the throughput of gene function interrogation by orders of magnitude, reported the presentation of data on tumor reactivity in various applications via its PathFinder DNA AssemblyTM technology in three posters at the 37th Annual Meeting of the Society for Immunology of Cancer (SITC) (Free SITC Whitepaper) in Boston, Massachusetts (Press release, RootPath, NOV 10, 2022, View Source [SID1234623767]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The posters that we are presenting at SITC (Free SITC Whitepaper) continue to demonstrate the power of RootPath’s platform and approach to transformative cell therapies," said Xi Chen, Co-founder and CEO of RootPath. "This showcases the efficiency and unmet need for our PathFinder DNA AssemblyTM technology along with its potential to target various tumor types through multiple applications. We are pleased that data continue to validate our platform, which can identify tumor reactive TCRs at unprecedented scale."

The first presentation provides an overview of an unbiased survey of tumor reactivity and the transcriptional landscape of 1,000 clones of PD-1hi T-cells from peripheral blood during ICB treatment and reveals the breadth and dynamics of anti-tumor immunity. Previous studies have demonstrated that PD-1 may be a biomarker for tumor reactive T-cells in peripheral blood. Using its novel PathFinder DNA AssemblyTM technology, RootPath surveyed 1,000 TCRs from peripheral bulk and PD-1hi T-cells from a melanoma patient before and after ICB treatment. Data show that validated tumor-reactive TCRs do not reside in a single scRNA-Seq cluster and are present before and after ICB therapy. These experiments, enabled by RootPath’s technology, enable the high-throughput discovery of tumor reactive TCRs from the blood and build the foundation for a personalized cell therapy that does not rely on access to the tumor.

The second presentation covers rapid discovery of personalized TCRs through a single-cell transcriptomic signature predicting tumor reactivity. The ideal cell therapy is potent, polyclonal, and proliferative while still being efficient to manufacture. To enable this, RootPath uses its TCR synthesis, screening technology, and reactivity database to develop a gene signature, Interpreter, that predicts tumor reactivity from single cell sequencing data. The company demonstrates the ability of Interpreter to accurately call tumor reactive T cells in a liver cancer patient and validate the TCR reactivity by ELISpot assays, and also shows the utility of Interpreter to quickly identify tumor-reactive TCRs without experimentation for a synthetic TIL product that is highly enriched for reactivity and in an improved cell phenotype.

The third presentation showcases antigen-agnostic discovery of tumor-reactive TCRs powered by repertoire-scale TCR gene synthesis and the use of banked allogeneic cancer cell lines revealing anti-tumor responses. The rare tumor-reactive T cells within the tumor-infiltrating lymphocyte (TIL) population are mediators of natural and therapy-induced anti-tumor responses. The enhancement and expansion of these elusive cells became a focus of recent innovations in immuno-therapy. However, most approaches focus on neoantigen-reactive T cells and overlook the equally important T cells that recognize wildtype tumor-associated antigens (TAAs) partly because most TAAs are yet to be discovered. RootPath established a method to screen thousands of TIL-derived TCRs against banked allogeneic tumor cell lines, which likely express many known and unknown TAAs that are expressed by the patient’s autologous tumor. A key to this method is to "HLA-personalize" the allogeneic tumor cell lines. RootPath has successfully identified multiple TCRs that are reactive to both autologous tumor and multiple cell lines.