Targeting CD45 with an Amanitin Antibody-Drug Conjugate Effectively Depletes Human HSCs and Immune Cells for Transplant Conditioning

ConclusionThese results demonstrate that targeting CD45 with an amanitin ADC results in potent in vitro and in vivo human HSC and immune cell depletion. This new CD45-AM ADC also significantly reduced disease burden in multiple leukemia models. Our results indicate Fc-silencing may avoid infusion-related toxicities observed with previous CD45 mAbs. An alpha-amanitin ADC targeted to CD45 may be appropriate for preparing patients for BMT since we hypothesize it may i) be non-genotoxic; ii) effectively deplete both HSC and immune cells; iii) avoid bystander toxicity, due to amanitin's poor cell permeability as a free toxin; and iv) kill cycling and non-cycling cells, the latter being necessary for effective HSC depletion. As our anti-CD45 ADCs are cross-reactive, we are currently investigating their HSC and immune cell depletion activity in vivo in NHPs to enable further preclinical development of these transplant conditioning agents.DisclosuresPalchaudhuri: Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties; Harvard University: Patents & Royalties. Pearse: Magenta Therapeutics: Employment, Equity Ownership, Patents & Royalties. Proctor: Magenta Therapeutics: Employment, Equity Ownership. Hyzy: Magenta Therapeutics: Employment, Equity Ownership. Aslanian: Magenta Therapeutics: Employment, Equity Ownership. McDonough: Magenta Therapeutics: Employment, Equity Ownership. Sarma: Magenta Therapeutics: Employment, Equity Ownership. Brooks: Magenta Ther...
Source: Blood - Category: Hematology Authors: Tags: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster III Source Type: research