6p4y

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

Structural highlights

6p4y is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.799Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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-7Ralpha chain and chimerized with human IgG1 constant regions. Crystal structures demonstrate that the two MAbs bound different IL-7Ralpha 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-7Ralpha, and MAb treatment is effective against relapsing disease, suggesting the use of anti-IL7Ralpha MAbs in relapsed T-ALL patients or patients that do not respond to chemotherapy.

New anti-IL-7Ralpha monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models.,Hixon JA, Andrews C, Kashi L, Kohnhorst CL, Senkevitch E, Czarra K, Barata JT, Li W, Schneider JP, Walsh STR, Durum SK Leukemia. 2019 Aug 22. pii: 10.1038/s41375-019-0531-8. doi:, 10.1038/s41375-019-0531-8. PMID:31439943[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Hixon JA, Andrews C, Kashi L, Kohnhorst CL, Senkevitch E, Czarra K, Barata JT, Li W, Schneider JP, Walsh STR, Durum SK. New anti-IL-7Ralpha monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models. Leukemia. 2019 Aug 22. pii: 10.1038/s41375-019-0531-8. doi:, 10.1038/s41375-019-0531-8. PMID:31439943 doi:http://dx.doi.org/10.1038/s41375-019-0531-8

6p4y, resolution 1.80Å

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