{
  "abstract": "Background: Therapeutic monoclonal antibodies are promising tools for the treatment of acute lymphoblastic leukemia (ALL). Our group previously developed a murine anti-IL-7Rα antibody (mAb#1) capable of recognizing IL-7Rα on leukemic cells. However, murine antibodies may induce immunogenic responses, limiting their clinical use and supporting the need for humanization. Aim: To generate and characterize a humanized version of mAb#1, termed HumAb#1, using CDR grafting, and to evaluate its structural conservation, antigen recognition, effects on intracellular signaling, and in vivo antileukemic activity. Materials and methods: Human germline sequences were selected as acceptor frameworks, and the CDRs of mAb#1 were grafted onto these sequences. Strategic backmutations were introduced to preserve structural and functional features related to antigen recognition. The humanized heavy and light chains were expressed in ExpiCHO-S cells. Structural conservation was assessed by modeling and alignment. Antigen recognition was evaluated by dot blot, flow cytometry, and binding assays using recombinant IL-7Rα. The effects of HumAb#1 on IL-7-induced signaling were analyzed by Western blot for phosphorylated STAT5, ERK1/2, and AKT. Antileukemic activity was evaluated in NSG mice xenografted with RS4;11 cells. Results: HumAb#1 showed high structural conservation relative to the parental antibody, with an RMSD of 0.422 Å. Flow cytometry demonstrated selective recognition of IL-7Rα-positive cells, with no detectable binding to negative cells. Assays using the recombinant receptor confirmed preservation of antigen recognition. HumAb#1 enhanced IL-7-induced signaling, with increased phosphorylation of STAT5, ERK1/2, and AKT. Despite this in vitro effect, treatment with HumAb#1 reduced leukemia burden in NSG mice xenografted with RS4;11 cells, as assessed by bioluminescence imaging. Discussion: Preservation of antigen recognition after humanization indicates that the CDR-grafting and backmutation strategy maintained important structural features of the parental antibody. The increased IL-7-induced phosphorylation of STAT5, ERK1/2, and AKT observed in vitro, together with the reduction in leukemia burden in vivo, suggests that the antileukemic activity of HumAb#1 may involve mechanisms beyond direct inhibition of IL-7Rα signaling. This apparent dissociation between signaling modulation and therapeutic activity highlights the need for further investigation of its mechanism of action. Conclusion: HumAb#1 retained structural and antigen-recognition properties of the parental antibody and demonstrated in vivo antileukemic activity, supporting further mechanistic and preclinical investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Centro de Pesquisa Boldrini (CPB), Campinas, SP, Brazil",
    "Universidade de Brasília (UnB), Brasília, DF, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Joey Ramone Ferreira FONSECA"
    },
    {
      "affs": [
        0
      ],
      "name": "Fernando Mesquita de Sousa de LIMA"
    },
    {
      "affs": [
        0
      ],
      "name": "João Mateus Silva FEITOZA"
    },
    {
      "affs": [
        0
      ],
      "name": "Aryanny Paula Sousa FERREIRA"
    },
    {
      "affs": [
        1
      ],
      "name": "Marcelo de Macedo BRIGIDO"
    },
    {
      "affs": [
        0
      ],
      "name": "Priscila Pini ZENATTI"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fc14jfvd78a7z.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107599",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926013465",
  "id": "fc14jfvd78a7z",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107599",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2739|Acute Lymphoblastic Leukemia research"
    ]
  ],
  "openalex": "W7223083051",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926013465/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fc14jfvd78a7z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:36Z",
      "native_id": "bf635005e7a84c63a4e86a2128f86fdb",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107599"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Acute Lymphoblastic Leukemia research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "HUMANIZATION AND FUNCTIONAL CHARACTERIZATION OF A MONOCLONAL ANTIBODY AGAINST THE INTERLEUKIN-7 RECEPTOR ALPHA CHAIN IN ACUTE LYMPHOBLASTIC LEUKEMIA",
  "title_text": "HUMANIZATION AND FUNCTIONAL CHARACTERIZATION OF A MONOCLONAL ANTIBODY AGAINST THE INTERLEUKIN-7 RECEPTOR ALPHA CHAIN IN ACUTE LYMPHOBLASTIC LEUKEMIA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:36Z",
  "url": "https://research.draconitic.com/paper/fc14jfvd78a7z",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}