TCR Cell Therapy Targeting MAGE-A1

Technology Overview

The MAGE family are CTAs expressed in many tumor types and MAGE-A1 has been shown to directly drive tumorigenesis. Specifically, MAGE-A1 is expressed in about 50% of multiple myeloma, up to 60% in triple negative breast cancer, 30% in non-small cell lung cancer and up to 50% in ovarian cancer cells. Using a high throughput platform to identify high affinity native antigen-specific TCRs, investigators at Fred Hutch led by Dr. Chapuis have identified and generated engineered version of rare high affinity anti-MAGE-A1 TCRs specific that avoids some of the significant toxicity and off-target specificity seen using transgenic mice or amino acid substitutions in the HLA/peptide complex.  Preclinical validation of these MAGE-A1 TCRs displayed strong cytotoxicity towards MAGE-A1+ cell lines and furthermore are active in both CD4 and CD8 T cells, demonstrating their high affinity nature. IND enabling work and vector (LVV) manufacturing has been completed.

Applications

•         Treatment or relapse prophylaxis for multiple myeloma, TNBC, NSCLC, melanoma (including basalioma), ovarian, colon cancer. 

Advantages

•         MAGE-A1 expression is strictly limited to testis and tumor tissue which minimizes likelihood of on target off tumor toxicities
•         HLA-A2 restricted MAGE-A1 peptide is unique to MAGE-A1
•         Transduction of CD8αβ co-receptor utilizes both CD4+ and CD8+ cells 

Patent Information

• US and Foreign Patent Applications Pending

Market Overview

• Globally, the multiple myeloma therapeutics market is estimated to be growing at a CAGR of 4.8% during the forecast period. The market's size is predicted to be USD 10.48 billion by 2027 from USD 8.29 billion in 2022.

Investigator Overview

• Aude Chapuis, MD, Clinical Research Division