Data from Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma
Year: 2025
Type: other
Abstract: Diffuse midline gliomas (DMG) are devastating brain tumors that occur primarily in children. The salient feature of these tumors is the presence of a H3K27M mutation (K27M), associated with the worst prognosis. Development of effective strategies for treating K27M+ DMG is desperately needed to help improve patient outcomes. In this study, we identified the cell surface antigen CD99 as notably expressed in DMGs, particularly in K27M+ DMGs. The increased expression of CD99 in K27M+ DMGs was a result of the oncohistone K27M mutation. In K27M+ DMG cells, CD99 inactivation impaired tumor growth by inducing cell differentiation. The development of a therapeutic anti-CD99 chimeric antibody, 10D1, with a membrane-proximal binding epitope enabled the evaluation of the antitumor efficacy of targeting CD99 in preclinical models of K27M+ DMGs. 10D1 suppressed DMG growth in vitro and in vivo by inducing apoptosis. When combined with radiation treatment, 10D1 exhibited improved antitumor efficacy and prolonged xenograft survival. Together, these findings provide a strong justification for the clinical development of 10D1 as a therapy for targeting CD99 to treat DMGs. Significance: The H3K27M mutation in diffuse midline glioma increases CD99 expression to suppress apoptosis, inhibit differentiation, and induce radioresistance, supporting using the anti-CD99 antibody 10D1 in pediatric brain cancer trials.
Authors: Ilango Balakrishnan, Krishna Madhavan, Angela Pierce, Joshua Michlin, Breauna Brunt, Senthilnath Lakshmanachetty, Dong Wang, John DeSisto, Zachary James Nuss, Nathan Davidson, Faye Walker, Ammu Suresh, Andrew Donson, Bridget Sanford, Kenneth L. Jones, Etienne P. Danis, Siddhartha S. Mitra, Adam L. Green, Nathan Dahl, Rajeev Vibhakar, Sujatha Venkataraman
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4413381872