AM109, a PSMA×CD137 bispecific antibody with target-dependent T cell activation and potent anti-tumor activity in prostate cancer
Presenter: Dong-Wook Kim, PhD Session: Redefining Targeted Therapy: Bispecific T-Cell Engagers and Antibody-Drug Conjugates 1 Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Dong-Wook Kim , Hyun-Jong Lee , Seong Yeol Kim , Min Yoon , Youngha Lee , In-Sik Hwang , Yoon Lee , Jong-Hoon Kim , Jong-Seo Lee AbClon, Seoul, Korea, Republic of
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) remains a fatal malignancy with limited responsiveness to current immunotherapies. To achieve tumor-restricted immune activation, we developed AM109, a bispecific antibody that links a PSMA-targeting humanized antibody to a CD137 (4-1BB) affibody, designed to activate T cells exclusively in the presence of PSMA-expressing tumor cells. AM109 elicited robust CD8⁺ T-cell activation and cytokine secretion (IFN-γ, IL-2, and Granzyme B) in PSMA⁺ LNCaP cells, but not in PSMA⁻ MKN45 cells, confirming its target-dependent mode of action. Cytotoxicity assays demonstrated dose-dependent tumor cell killing that correlated with PSMA expression levels. In vivo efficacy was evaluated using human CD137 transgenic mice bearing hPSMA/MC38 tumors, where AM109 achieved complete tumor regression at doses of 0.1-0.3 mpk, exhibiting superior potency compared with the reference CD137 agonist utomilumab. Structural and functional stability were maintained for at least 12 weeks at 4-40 °C. Pharmacokinetic and single-dose toxicity studies in rodents revealed favorable systemic exposure and good tolerability. Collectively, these findings demonstrate that AM109 selectively activates T cells within the tumor microenvironment, eliciting potent and PSMA-dependent anti-tumor responses with an improved therapeutic window. AM109 therefore represents a promising next-generation immunotherapeutic candidate for the treatment of mCRPC.
Disclosure
D. Kim, None.. H. Lee, None.. S. Kim, None.. M. Yoon, None.. Y. Lee, None.. I. Hwang, None.. Y. Lee, None.. J. Kim, None.. J. Lee, None.
Cited in
Control: 1081 · Presentation Id: 9641 · Meeting 21436