Masked T Cell Engagers
About T Cell Engagers
T cell engagers are designed to redirect immune effector cells against cancer cells by simultaneously binding to a specific tumor-associated antigen expressed on the cancer cells and the T cell receptor complex on T cells. To date, T cell engagers have demonstrated significant promise for cancer immunotherapy in a variety of advanced solid tumors, but the potential has been limited by toxicity.
Xilio’s Masked T Cell Engagers
We are currently leveraging our proprietary, clinically-validated masking technology to advance two wholly-owned programs for masked T cell engagers, as well as an additional program in collaboration with AbbVie.
Our masked T cell engagers include molecules with one or more tumor-associated antigen (TAA) binding domains and a CD3 targeting domain, which are designed to release a potent, short half-life T cell engager upon tumor-selective activation (ATACR format), and molecules that include a co-stimulatory domain designed to further enhance potency and durability of the T cell response (SEECR format).
Depending on the desired properties that we are seeking to achieve for a particular molecule and TAA(s), our modular architecture for masked T cell engagers enables optionality to:
- include multiple TAA binding domains;
- add a co-stimulatory domain; and/or
- mask the CD3 targeting domain, TAA binding domain(s) and/or the co-stimulatory signaling domain.
Potential first-in-class dual-targeted masked T cell engager targeting PSMA and STEAP1 with built-in co-stimulatory signaling (SEECR format)
PSMA and STEAP1 are expressed in most prostate cancer tumors, and targeting both of these TAAs has the potential to address tumor heterogeneity while minimizing the potential for resistance due to antigen escape.
We expect to nominate a development candidate in the second quarter of 2026 and submit an IND application in 2027.
Potential first-in-class masked T cell engager targeting CLDN18.2
CLDN18.2 is expressed in gastrointestinal cancers (including gastric, pancreatic and esophageal) and lung cancer.
Our modular design architecture for T cell engagers also enables flexibility to evaluate designs that incorporate masking of the CLDN18.2 binding domain and/or add a co-stimulatory domain (SEECR format) in parallel with advancing the current molecule design.
We expect to submit an IND application in 2027.
Masked T Cell Engager Presentations & Publications
04/17/2026
Masked T Cell Engagers (XTX601) Poster Presentation at the American Association for Cancer Research (AACR) 2026 Annual Meeting
Discovery and Optimization of XTX601, a Masked Claudin 18.2-Targeting T Cell Engager
11/07/2025
Masked T Cell Engagers Poster Presentation at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting
Masked T Cell Engagers Designed to Drive Potent Synthetic Anti-Tumor Immunity with Favorable Tolerability
11/07/2024
Tumor Activated Cell Engager Poster Presentation at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting
Tumor-activated immune cell engagers designed to drive synthetic immunity against cancer demonstrated protease-dependent activation and robust anti-tumor activity in preclinical models