主权项 |
1. A molecular construct comprising,
a pair of CH2-CH3 segments of an IgG.Fc; a pair of effector elements, wherein each effector element is an immune checkpoint protein, an antibody fragment specific for CD25, or a drug bundle comprising a plurality of immunosuppressant molecules; and a pair of targeting elements, wherein each targeting element is an antibody fragment specific for a human leukocyte antigen (HLA) allotype present only on cells of a donor transplant, wherein, when each effector element is the immune checkpoint protein, then the pair of effector elements is linked to the N-termini of the pair of CH2-CH3 segments, and the pair of targeting elements is linked to the C-termini of the pair of CH2-CH3 segments, or vice versa, when each effector element is the antibody fragment specific for CD25, then (1) the pair of effector elements is linked to the N-termini of the pair of CH2-CH3 segments, and the pair of targeting elements is linked to the C-termini of the pair of CH2-CH3 segments, or vice versa, or (2) when the pair of effector elements and the pair of targeting elements are both in the form of single-chain variable fragments (scFvs), then the pair of targeting elements is linked to the N-termini of the pair of effector elements in a tandem or diabody configuration, thereby forming a pair of bispecific scFvs that are linked to the N-termini of the pair of CH2-CH3 segments, or when each effector element is the drug bundle, then the pair of effector elements is linked to the C-termini of the pair of CH2-CH3 segments, and the pair of targeting elements is linked to the N-termini of the pair of CH2-CH3 segments. |