6P67
Crystal Structure of a Complex of human IL-7Ralpha with an anti-IL-7Ralpha 2B8 Fab
Summary for 6P67
| Entry DOI | 10.2210/pdb6p67/pdb |
| Descriptor | Anti-IL-7R 2B8 Fab heavy chain, anti-IL-7R 2B8 Fab light chain, Interleukin-7 receptor subunit alpha, ... (7 entities in total) |
| Functional Keywords | interleukin-7 receptor extracellular dohmain, antibody 2b8 fab fragment, protein polymer, immune system |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 12 |
| Total formula weight | 296908.01 |
| Authors | Walsh, S.T.R.,Kashi, L.,Kohnhorst, C.L. (deposition date: 2019-06-03, release date: 2019-09-04, Last modification date: 2024-10-23) |
| Primary citation | Hixon, J.A.,Andrews, C.,Kashi, L.,Kohnhorst, C.L.,Senkevitch, E.,Czarra, K.,Barata, J.T.,Li, W.,Schneider, J.P.,Walsh, S.T.R.,Durum, S.K. New anti-IL-7R alpha monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models. Leukemia, 34:35-49, 2020 Cited by PubMed Abstract: Pediatric T cell acute lymphoblastic leukemia (T-ALL) cells frequently contain mutations in the interleukin-7 (IL-7) receptor pathway or respond to IL-7 itself. To target the IL-7 receptor on T-ALL cells, murine monoclonal antibodies (MAbs) were developed against the human IL-7Rα chain and chimerized with human IgG1 constant regions. Crystal structures demonstrate that the two MAbs bound different IL-7Rα epitopes. The MAbs mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against patient-derived xenograft (PDX) T-ALL cells, which was improved by combining two MAbs. In vivo, the MAbs showed therapeutic efficacy via ADCC-dependent and independent mechanisms in minimal residual and established disease. PDX T-ALL cells that relapsed following a course of chemotherapy displayed elevated IL-7Rα, and MAb treatment is effective against relapsing disease, suggesting the use of anti-IL7Rα MAbs in relapsed T-ALL patients or patients that do not respond to chemotherapy. PubMed: 31439943DOI: 10.1038/s41375-019-0531-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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