7QPJ

Crystal structure of engineered TCR (756) complexed to HLA-A*02:01 presenting MAGE-A10 9-mer peptide

Summary for 7QPJ

• Entry DOI: 10.2210/pdb7qpj/pdb
• Related: 7PBC 7PDW 7PDX
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Melanoma-associated antigen 10, ... (7 entities in total)
• Functional Keywords: t-cell receptor, human leukocyte antigen, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 95289.79

Authors

Simister, P.C.,Border, E.C.,Vieira, J.F.,Pumphrey, N.J. (deposition date: 2022-01-04, release date: 2022-08-03, Last modification date: 2024-11-06)

Primary citation

Simister, P.C.,Border, E.C.,Vieira, J.F.,Pumphrey, N.J.
Structural insights into engineering a T-cell receptor targeting MAGE-A10 with higher affinity and specificity for cancer immunotherapy.
J Immunother Cancer, 10:-, 2022

PubMed Abstract: T-cell receptor (TCR) immunotherapy is becoming a viable modality in cancer treatment with efficacy in clinical trials. The safety of patients is paramount, so innovative cell engineering methods are being employed to exploit adaptive immunity while controlling the factors governing antigen receptor (ie, TCR) specificity and cross-reactivity. We recently reported a TCR engineering campaign and selectivity profiling assay (X-scan) targeting a melanoma antigen gene (MAGE)-A10 peptide. This helped to distinguish between two well-performing TCRs based on cross-reactivity potential during preclinical drug evaluation, allowing one to be advanced to T-cell immunotherapeutic clinical trials. Here, we present three-dimensional structural information on those TCRs, highlighting engineering improvements and molecular mechanisms likely underpinning differential selectivity.

PubMed: 35851311
DOI: 10.1136/jitc-2022-004600

Experimental method

X-RAY DIFFRACTION (1.54 Å)