Structural highlights
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.
References
- ↑ 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
