KK2845 is a non-fucosylated fully human monoclonal antibody targeting TIM-3, conjugated with the PBD payload SG3199
- Anti-TIM-3 antibody conjugated to SG3249
at cysteines - SG3249 consists of a PEG-8 spacer, a valine-alanine
linker, and PBD dimer warhead SG3199 - Cathepsin in the lysosome compartment cleaves
the valine-alanine linker to release the warhead
KK2845 localization and trafficking
Green: KK2845-Alexa488
Red: Lysosome
Blue: Nuclear
KK2845 is an ADC that delivers
the cytotoxic warhead, SG3199,
to TIM-3-expressing cells
- SG3199 is a highly potent DNA cross-linking PBD dimer that has been reported to be cytotoxic
- TIM-3 is expressed on LSCs and blast cells in patients with AML, but not on normal HSCs
- Therefore, targeting SG3199 to TIM-3 may help avoid severe myelosuppression, as target antigens are restricted to tumor cells
Images used with permission from Zou J et al. Leukemia. 2025 under creative commons license CC BY-NC-ND 4.0. Available at http://creativecommons.org/licenses/by-nc-nd/4.0/. Accessed 14 May, 2026.
AML, acute myeloid leukemia; ADC, antibody-drug conjugate; HSC, hematopoietic stem cell; LSC, leukemia stem cell; PBD, pyrrolobenzodiazepine; PEG-8, polyethylene glycol-8; TIM-3, T-cell immunoglobulin mucin-3.
Reference: Zou J et al. Leukemia. 2025;39(8):1848-1856.