Anti-TYRP1 Bi-specific T cell Engager for Treatment of TYRP1-expressing melanoma

NU 2022-123

INVENTORS

  • Irina Balyasnikova (Feinberg School of Medicine, Department of Neurological Surgery)*
  • Isabelle Le Poole (Feinberg School of Medicine, Department of Dermatology)*

SHORT DESCRIPTION
A bispecific T cell engager that targets CD3+ T cells and TYRP1-expressing melanoma cells.
Fold-change in tumor size in mice following subcutaneous injection of 888 A2 melanoma cells and treatment with a combination of the TYRP1 BTE and T cells or left untreated. Change in tumor size is shown from the onset of treatment, and the arrow indicates the repeat treatment date. TYRP1 BTE promotes T cell-mediated tumor growth suppression in vivo.
BACKGROUND
Melanoma is the deadliest form of skin cancer with an estimated 105,000 new cases and around 8,430 deaths expected in the United States in 2025. It is a UV-promoted form of skin cancer that readily metastasizes, and in patients in which metastasis has occurred, the survival rate is only 65% when the disease has spread to lymph nodes and 25% when distant spread has occurred. Current treatments for melanoma face high costs, poor specificity, limited effectiveness, and significant side effects; therefore, there is a clear unmet need for improved methods to target melanoma while minimizing adverse side effects.  Melanoma is commonly infiltrated by T cells, a phenomenon known as a “hot tumor" which refers to cancer that has already triggered a strong immune response, has been infiltrated by immune cells like T cells, and is likely to respond well to immunotherapy. Bispecific T cell engagers (BiTEs) are a new type of immunotherapy which, when a tumor-specific cell surface antigen can be identified, can brings a patient's T-cells close to the cancer cells and activate the T-cells to kill the cancer. Tyrosinase-related protein 1 (TYRP1) is the most abundant protein expressed by melanocytic cells, and in melanoma tumor cells, the protein was recently shown to be partially trafficked to the cell surface. A novel therapeutic approach that exploits these characteristics of melanoma could address this unmet need and significantly improve clinical outcomes for patients.

ABSTRACT
Northwestern researchers have developed a BiTE designed to target CD3ε expressed on the surface of T cells and TYRP1 expressed on the surface of melanoma cells. This innovative approach has been shown to trigger potent cytotoxic responses against melanoma cells with minimal damage to healthy tissues in vitro and in vivo evaluation in preclinical models have demonstrated its ability to mediate effective tumor cell killing. This therapeutic modality supports a simpler streamlined manufacturing process for an off-the-shelf product.


DEVELOPMENT STAGE
Early Preclinical - In Vivo PoC Data Available.

APPLICATIONS

  • Immunotherapy for melanoma: Applicable to both cutaneous and metastatic melanoma, including brain metastases.

ADVANTAGES

  • Improved specificity and safety: Minimizes potential side effects through targeted action.
  • Overcomes immune evasion: Activates T cells independent of traditional activation pathways.
  • Potent immune response: Induces strong cytotoxicity against melanoma cells, including bystander killing.
  • Fast manufacturing: Simplifies production with an off-the-shelf format for rapid deployment.

PUBLICATIONS

IP STATUS
US patent pending (19/103,495).

CATEGORY/INDUSTRY PIPELINE
Therapeutics

KEYWORDS
Therapeutics, cancer, oncology, melanoma, immunotherapy, bispecific T cell engager, TYRP1, CD3, targeted therapy, off-the-shelf, biologic

Patent Information: