A novel T-cell engaging Bi-specific antibody targeting the leukemia antigen PR1/HLA-A2

Amanda C. Herrmann, Jin S. Im, Sumedha Pareek, Wilfredo Ruiz-Vasquez, Sijie Lu, Anna Sergeeva, Jennifer Mehrens, Hong He, Gheath Alatrash, Pariya Sukhumalchandra, Lisa St John, Karen Clise-Dwyer, Dongxing Zha, Jeffrey J. Molldrem

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Despite substantial advances in the treatment of acute myeloid leukemia (AML), only 30% of patients survive more than 5 years. Therefore, new therapeutics are much needed. Here, we present a novel therapeutic strategy targeting PR1, an HLA-A2 restricted myeloid leukemia antigen. Previously, we have developed and characterized a novel T-cell receptor-like monoclonal antibody (8F4) that targets PR1/HLA-A2 and eliminates AML xenografts by antibody-dependent cellular cytotoxicity (ADCC). To improve the potency of 8F4, we adopted a strategy to link T-cell cytotoxicity with a bi-specific T-cell-engaging antibody that binds PR1/HLA-A2 on leukemia and CD3 on neighboring T-cells. The 8F4 bi-specific antibody maintained high affinity and specific binding to PR1/HLA-A2 comparable to parent 8F4 antibody, shown by flow cytometry and Bio-Layer Interferometry. In addition, 8F4 bi-specific antibody activated donor T-cells in the presence of HLA-A2+ primary AML blasts and cell lines in a dose dependent manner. Importantly, activated T-cells lysed HLA-A2+ primary AML blasts and cell lines after addition of 8F4 bi-specific antibody. In conclusion, our studies demonstrate the therapeutic potential of a novel bi-specific antibody targeting the PR1/HLA-A2 leukemia-associated antigen, justifying further clinical development of this strategy.

Original languageEnglish (US)
Article number3153
JournalFrontiers in immunology
Volume10
Issue numberJAN
DOIs
StatePublished - 2019

Keywords

  • Acute myeloid leukemia
  • Bi-specific antibody
  • Cancer immunotherapy
  • PR1
  • Re-directed cytotoxicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

MD Anderson CCSG core facilities

  • Monoclonal Antibody Facility
  • Flow Cytometry and Cellular Imaging Facility

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