On December 27, 2023 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315) and CtM Biotech (Shanghai) Co., Ltd ("CtM Bio") reported that the development of a tri-specific T cell engager for an intracellular target achieved milestone progress (Press release, Biocytogen, DEC 27, 2023, View Source [SID1234638812]). In just one year since the start of the collaboration, the companies have identified a WT1/HLA-A02-specific T cell engager (WT1xCD3x4-1BB tri-specific antibody) with outstanding preclinical anti-tumor activities for both hematological malignancies and solid tumors. The incorporation of the T co-stimulatory signal for WT1-targeting T cell engager further gives it the best-in-class properties and first-in-class potential. Its preclinical data has been accepted for presentation at the upcoming 2024 AACR (Free AACR Whitepaper) annual meeting.
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WT1 (Wilms’ tumor gene 1) is an intracellular protein highly enriched in certain cancer cells compared to normal tissues, making it an attractive tumor target for cancer immunotherapy. To identify novel WT1-targeting antibody-based therapeutics, Biocytogen harnessed its RenTCR-mimicTM mice and high-throughput in vivo and in vitro screening platforms to successfully generate WT1 antibodies with superior specificity and high affinity to the HLA/peptide complex. These antibodies were further engineered using CtM’s state-of-the-art T cell engager technology, which is specifically designed to overcome T cell over-activation toxicity and prevent T cell exhaustion, leading to highly effective, safe and controllable multi-specific engagers.
Dr. Yuelei Shen, President and CEO of Biocytogen, said, "Our collaborative efforts with CtM Bio have progressed rapidly, resulting in the identification of novel immunotherapies targeting WT1. This rapid and effective development of multi-specific T cell engagers undoubtedly validates CtM Bio’s advanced T-cell engager technology, along with our expertise in discovering fully human TCR-mimic antibodies against intracellular targets. We anticipate advancing this preclinical candidate into clinical trials soon, providing treatment options for patients with acute myeloid leukemia, ovarian cancer, and various solid tumors."
Dr. Lei Fang, Vice President of Lepu Biopharma and CEO of CtM Bio, said, "The combination of Biocytogen’s streamlined fully human antibody discovery capabilities and CtM Bio’s deep understanding of immune cell engagers have greatly accelerated our development of differentiated T cell engagers targeting WT1. We look forward to continued collaborations to further develop this candidate and initiate clinical trials. Together, we aim to usher in a new era of therapies targeting intracellular tumor antigens and broaden the applications of T cell engagers for the treatment of solid tumors, which will ultimately offer new opportunities for cancer patients."
About the TCR-Mimic Antibody Discovery Platform
Biocytogen’s TCR-Mimic platform focuses on the discovery of fully human antibodies to intracellular targets that are presented on the cell surface by MHC class I molecules. Leveraging proprietary RenTCR-mimicTM (HLA/RenMab) mice and specialized immunization protocols, Biocytogen’s platform is designed to generate TCR-mimic (TCRm) antibodies that are highly specific for peptide/HLA complexes and not HLA itself. Subsequently, Biocytogen’s high-throughput antibody screening platform aims to swiftly identify TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients to overcome tumor immune escape. Currently, antibody hits for multiple intracellular targets, including TAAs, cancer-testis antigens, mutated protein antigens, and viral protein antigens, are being evaluated in vivo and in vitro. Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies.
About the T-cell Engager Platform
T-cell engagers are typically bispecific antibodies with one targeting tumor-associated antigens (TAAs) and the other activating CD3 signal on T cells. The mechanisms involve promoting the formation of an immune synapse between T cells and cancer cells, activating T cells to induce the lysis of cancer cells. To overcome the limitations of existing T cell engagers, CtM Bio has developed a unique T cell engager platform called TOPAbody. By introducing T-cell co-stimulatory signal 4-1BB and finely tuning the affinity and activity of each module in the engager, TOPAbody allows for the effective enhancement of T cell cytotoxicity with minimal side effects. TOPAbody prolongs T cell lifespan and promotes T cell infiltration into tumors. Currently, several products from this platform have demonstrated outstanding anti-tumor activity, particularly showing significant promise for immunologically "cold" tumors that do not respond to PD-1 treatment.