Details

Autor(en) / Beteiligte

• Parameswaran, Neetha
• Luo, Liping
• Zhang, Lingjun
• Chen, Joel
• DiFilippo, Frank P.
• Androjna, Charlie
• Fox, David A.
• Ondrejka, Sarah L.
• Hsi, Eric D.
• Jagadeesh, Deepa
• Lindner, Daniel J.
• Lin, Feng

Titel

CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma

Ist Teil von

• Leukemia, 2023-10, Vol.37 (10), p.2050-2057

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• T cell lymphomas (TCL) are heterogeneous, aggressive, and have few available targeted therapeutics. In this study, we determined that CD6, an established T cell marker, was expressed at high levels on almost all examined TCL patient specimens, suggesting that CD6 could be a new therapeutic target for this life-threatening blood cancer. We prepared a CD6-targeted antibody-drug conjugate (CD6-ADC) by conjugating monomethyl auristatin E (MMAE), an FDA-approved mitotic toxin, to a high-affinity anti-human CD6 monoclonal antibody (mAb). In contrast to both the unconjugated anti-CD6 mAb, and the non-binding control ADC, CD6-ADC potently and selectively killed TCL cells in vitro in both time- and concentration-dependent manners. It also prevented the development of tumors in vivo in a preclinical model of TCL. More importantly, systemic or local administration of the CD6-ADC or its humanized version, but not the controls, significantly shrank established tumors in the preclinical mouse model of TCL. These results suggest that CD6 is a novel therapeutic target in TCLs and provide a strong rationale for the further development of CD6-ADC as a promising therapy for patients with these potentially fatal lymphoid neoplasms.