Anti-CD99 Antibodies Cytotoxic to Leukemia

Technology Overview

The Koide Lab at NYU Langone Health has developed new anti-CD99 antibodies for the treatment of rare hematological malignancies. These antibodies possess several features advantageous for drug development: fully human framework and IgG formatted. PoC studies (Romero et al. JMB 2021) show these antibodies to bind endogenously-expressed CD99 with nanomolar affinity and high specificity (no off-target binding to CD99 homologs). Moreover, exogenous addition of these antibodies induces cytotoxicity in T-cell acute lymphoblastic leukemia (T-ALL) cell lines and T-ALL patient samples without toxicity to the PBMC of healthy donor samples.

Background

CD99 is a type-1 transmembrane protein that is upregulated in many types of cancers including, hematopoietic and bone malignancies. Prior work (Chung et al. Sci Transl Med 2017) has established CD99 as a therapeutic target for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). In this study, a mouse monoclonal antibody targeting CD99 in AML and MDS cell lines induced apoptosis independent of immune effector function (ADCC and ADCP). In a different study (Pettersen et al. J Immunol. 2001), an anti-CD99 antibody induced apoptosis of a T-ALL cell line. Despite strong proof-of-concept (PoC) data, these antibodies are in IgM format thereby limiting their potential to be manufactured into therapeutics.

Development Status

The NYU inventors have engineered improved anti-CD99 antibody clones with greater affinity and cytotoxicity. The lead clone is presently being tested for in vivo functional efficacy in a T-ALL xenograft mouse model.

Applications

• Hematologic cancers
• T-ALL
• AML
• MDS
• Other potential cancer subtypes
  
• Triple negative breast cancer
• Colon cancer
• Prostate cancer
• Synovial sarcoma
• Ewing’s sarcoma
• Diagnostic tool
• Detect CD99 as a biomarker
• Basic biology research
• MoA of CD99

Advantages

• Drug target
  
• The CD99 is cell-surface exposed and accessible to antibody drugs
• High affinity and specificity
  
• Nanomolar affinity and high specificity
• On-target, on-tissue toxicity independent of immune effector function
  
• Large anticipated therapeutic window
  
• No toxicity to healthy donor samples

IP Status

NYU has filed a PCT patent application covering the antibody sequences (including improved clones) and their uses.