6P4Y

Crystal Structure of anti-IL-7Ralpha 4A10 Fab

Summary for 6P4Y

• Entry DOI: 10.2210/pdb6p4y/pdb
• Descriptor: 4A10 Fab heavy chain, 4A10 Fab light chain (3 entities in total)
• Functional Keywords: antibody 4a10 fab fragment, protein polymer, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47966.46

Authors

Walsh, S.T.R.,Kashi, L.,Kohnhorst, C.L. (deposition date: 2019-05-29, release date: 2019-09-04, Last modification date: 2024-11-20)

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

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: 31439943
DOI: 10.1038/s41375-019-0531-8

Experimental method

X-RAY DIFFRACTION (1.799 Å)