Description:
TCR Cell Therapy Targeting MAGE-A1
High-affinity MAGE-A1-specific TCR for the treatment of multiple myeloma and solid tumors.
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.
<ul>
<li>Treatment or relapse prophylaxis for multiple myeloma, TNBC, NSCLC, melanoma (including basalioma), ovarian, colon cancer. </ul>
<ul>
<li> MAGE-A1 expression is strictly limited to testis and tumor tissue which minimizes likelihood of on target off tumor toxicities</li>
<li> HLA-A2 restricted MAGE-A1 peptide is unique to MAGE-A1</li>
<li> Transduction of CD8αβ co-receptor utilizes both CD4+ and CD8+ cells </li>
</ul>
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.
Aude Chapuis, MD, Clinical Research Division
IND enabling
US and Foreign Patent Applications Pending
17079ChapuisMAGEA1.pdf
MAGE | T-cell | TCR | T cell receptors | MAGEA1 | TNBC | OC | TCRs | Megan McAfee | Thomas Schmitt | NSCLC | tetramer | HLA-matched | tumor | tumour | CD8 | CD4 | effector | helper | CT antigens | Melanoma-associated antigen 1 | tumorigenesis | cancer | oncology | neoplasm |
mage-a1-tcr-17-079
