A Phase I study of an HLA-DPB1*0401-restricted T cell receptor targeting MAGE-A3 for patients with metastatic cancers

Background Adoptive transfer of genetically-modified T cells is being explored as a salvage treatment for patients with selected metastatic cancers. Most of the current strategies utilize MHC class I-restricted T cell receptor (TCR) or chimeric antigen receptor (CAR) technologies to genetically modify CD8+ T cells or bulk T cells for patient treatment. Evidence indicates that CD4+ T cells can induce tumor regression, similar to CD8+ T cells. To test this hypothesis, an HLA-DPB1*0401-restricted TCR recognizing MAGE-A3 was isolated from a patient’s peripheral blood after MAGE-A3 peptide vaccination. Because HLA-DPB1*0401 is present in 40~70% of the Caucasian population and MAGE-A3 is expressed in up to one third of tumor specimens from a variety of cancer types, this TCR immunotherapy can potentially be beneficial for a significant portion of cancer patients.