TCR Therapy Targeting MAGE-A4

Recently at the 2022 CTOS Conference, Adaptimmune announced the SPEARHEAD-1 clinical trial data of its T cell receptor-engineered T cell (TCR-T) therapy, Afamitresgene autoleucel (afami-cel), for synovial sarcoma. The results showed that the overall response rate of afami-cel was 39% and the median duration of response was 50 weeks [1]. Results show afami-cel can effectively activate and promote the infiltration of proliferative cytotoxic T cells into the tumor. The drug has completed and reached the primary clinical endpoint, bringing good news for TCR-T therapy.

Afami-cel is a TCR-T cell drug targeting MAGE-A4. It is an autologous T cell expressing a specific TCR that can recognize the MAGE-A4 230-239 (GVYDGREHTV) peptide restricted by HLA-A2 [2]. Given the specificity of TCR recognition depends heavily on the precise configuration of the peptide-MHC complex, having access to highly tailored MHC monomers and tetramers that accurately present the MAGE-A4 epitope is essential for optimizing TCR binding and improving functional assays. Utilizing an MHC complex custom service allows researchers to control key variables such as peptide loading and allele specificity, which can substantially influence the outcome of T cell response assessments and therapeutic validation. MAGE-A4 is a member of the MAGE-A subfamily of the melanoma antigen gene family. Its full name is Melanoma-associated antigen 4. It is highly expressed in a variety of tumor cells and low in normal tissue cells. It is a very attractive target for solid tumor cell therapy, especially TCR-T therapy.

Figure 1. MAGE-A4 Protein

KACTUS has a refined protein preparation technology and has successfully launched MHC polypeptide complex products of MAGE-A4, including MHC-MAGE-A4 polypeptide complex monomers and tetramers in different forms. These provide high-quality antigen research tools for cell therapy such as TCR-T, and assist customers in drug development and optimization. KACTUS also provides MHC polypeptide complexes of other target proteins, covering different popular targets such as MAGE-A3, AFP, NY-ESO-1, KRAS, p53, and Survivin.

Advantages of KACTUS MHC Peptide Complex Products

• Mammalian cell expression system for a more realistic conformation and better biological activity
• Does not require renaturation, greatly shortening the lead time
• Customized services for MHC peptide complexes can be provided including various species, various genotypes, various antigenic peptides, monomers/tetramers, biotinylated tetrameric complexes, fluorescent labeling complexes, etc.

MHC Monomers & Tetramers with MAGE-A4 Antigens

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