Disruptable linker compositions, switchable bispecific t cell nanoengager (switch-bite) compositions comprising the same, and methods of use thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsMichael J. Mitchell, Ningqiang Gong
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Abstract
The present disclosure provides switchable bispecific T cell engagers (switch-BiTEs or SiTEs). In certain embodiments, the switch-BiTEs comprise a disruptable linker. The present disclosure further relates to methods of treating cancer and methods of generating responses in vivo comprising use of the switch-BiTEs of the present disclosure.
Claims34
A disruptable linker comprising a compound of formula (I):
- wherein:
- A1 is
- A2 is
- Z1 and Z2 each independently comprise a cross-linking moiety;
- L1 and L2 each independently comprise a linker;
- B1 is selected from the group consisting of β-cyclodextrin (β-CD) and cucurbit[8]uril;
- B2 comprises a β-CD or curcurbit[8]uril binding moiety;
- * indicates the bond between L1 and B1;
- ** indicates the bond between L2 and B2;
- and
- bond a is an optional non-covalent bonding interaction.
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The method of claim 41, wherein:
- (a) A1 comprises
- (b) A2 comprises
- and
- (c) each occurrence of n is independently selected from the group consisting of 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 and 45.
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Dependencies are inferred from the claim text.