Antibody-Polymer Conjugates For Engaging T Cells To Destroy Cancer Cells

SUMMARY

An antibody linked to a polymer that connects T cells to cancer cells enabling broad cancer targeting and effective tumor cell killing without needing tumor-specific antigens

The Unmet Need: Novel therapeutics to effectively direct immune response again tumors that might otherwise remain undetected

• Immuno-oncology has revolutionized cancer treatment by harnessing the patient's own immune system to combat malignancies. A critical focus within this field is the development of T cell engagers, which are therapeutics designed to physically connect a patient's cytotoxic T cells directly to cancer cells. This forced proximity is essential because it facilitates the targeted destruction of malignant cells by the immune system. 

• Despite their promise, current T cell engagers, such as bispecific T cell engagers (BiTEs), face significant limitations due to their strict reliance on tumor-associated antigens (TAAs). These therapies require the identification and targeting of specific TAAs, meaning a unique molecule must be custom-developed for each cancer type, which severely complicates development and regulatory pipelines. Furthermore, many tumors employ evasion mechanisms by downregulating TAA expression or lacking the genetic variability needed to encode these immunogenic proteins. Consequently, these antigen-dependent therapies frequently lose their efficacy, highlighting the urgent problem of tumor evasion in current immunotherapies.

The Proposed Solution: Synthetic T cell engager antibody platform facilitating T-cell mediated cytotoxicity independent of tumor-associated antigens

• The faculty inventor developed the Synthetic T Cell Engager Antibody (SynTEA) platform designed to bridge a patient's T cells directly to cancer cells. This solution consists of an anti-CD3ε monoclonal antibody chemically conjugated to a pyridyl disulfide-containing polymer using strain-promoted azide-alkyne click chemistry. SynTEA employs a dual-targeting mechanism: the antibody component specifically binds to the CD3ε domain to activate T cells, while the polymer component binds to free surface thiols on cancer cells. By physically connecting these cells, the therapy stimulates robust T cell activation and drives the targeted cytotoxic destruction of malignant tumors.

• This technology is highly differentiated from conventional bispecific T cell engagers because it completely bypasses the reliance on tumor-associated antigens (TAAs). Traditional therapies require specific TAAs, making them vulnerable to tumor evasion when cancers downregulate these antigens. Instead, this solution exploits elevated surface thiols, a universal metabolic characteristic of the tumor microenvironment driven by upregulated thioredoxin activity. This TAA-independent approach allows a single therapeutic molecule to target a broad spectrum of cancer types. Consequently, it circumvents common resistance mechanisms and significantly streamlines drug development by eliminating the need for customized, cancer-specific molecules

ADVANTAGES

ADVANTAGES

• Enables broad-spectrum cancer targeting 
• Overcomes common tumor evasion mechanisms
• Facilitates a potent dual-targeting mechanism that simultaneously bridges T cells and cancer cells to drive robust T cell activation and targeted tumor destruction
• Streamlines drug development and regulatory processes by utilizing a universal targeting approach that does not require customization for individual cancer types
• Highly customizable and modular design- easy adjustments to polymer sizes, antibody clones, and conjugation ratios to optimize therapeutic efficacy

APPLICATIONS

• Next-generation T-cell engager

• Broad-spectrum cancer immunotherapy

• Solid tumor targeted therapy

• Hematological malignancy immunotherapy

• Antigen-independent tumor targeting

• Demonstrates strong preclinical efficacy, showing enhanced survival rates in models for both solid tumors (e.g., melanoma) and blood cancers (e.g., leukemia)