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AssigneeCue Biopharma, Inc.
InventorsRonald D. SEIDEL, III, John F. ROSS, Chee Meng LOW
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The present disclosure provides antigen presenting polypeptide comprising a TGF-β MOD that is reversibly masked and acts as a TGF-β receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The antigen-presenting poly peptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of diseases and disorders including autoimmune diseases, allergies, GVHD, HGVD, and metabolic disorder.
An unconjugated TMAPP comprising:
The unconjugated TMAPP of any preceding claim, wherein the presenting sequence or the presenting complex comprises:
The unconjugated TMAPP of any preceding claim, wherein at least one presenting sequence or presenting complex comprises:
The unconjugated TMAPP of any preceding claim, wherein the presenting sequence or a presenting complex comprises a disulfide bond formed between one of MHC α1 or α2 domain polypeptide sequence and one of the β1 or β2 domain polypeptide sequences.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, comprising a masked TGF-β MOD in cis.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein the TGF-β sequence is:
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein the TGF-β sequence is a TGF-β3 polypeptide optionally comprising a substitution of C77.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein at least one masking sequence is a TGF-β receptor (TOR) polypeptide, anti-TGF-β antibody or antibody-related polypeptide/aa sequence.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein at least one chemical conjugation site or additional chemical conjugation site is selected from the group consisting of:
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein the additional MOD (wt. or variant) or the additional pair of MODs (wt. or variant) are selected independently from the group consisting of IL-2, PD-L1, 4-1BBL polypeptide sequences and variants of any thereof. For example, the unconjugated TMAPP or unconjugated duplex TMAPP may comprise at least one IL-2 MOD (wt. or variant) and/or at least one PD-L1 (wt. or variant) polypeptide sequence(s).
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein the additional MOD (wt. or variant) or the additional pair of MODs (wt. or variant) comprise at least one IL-2 MOD (wt. or variant) polypeptide sequence, or at least one pair of IL-2 MOD (wt. or variant) polypeptide sequences in tandem.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, wherein the additional MOD (wt. or variant) or the additional pair of MODs (wt. or variant) comprise at least one PD-L1 MOD (wt. or variant) polypeptide sequence.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim wherein the additional MOD (wt. or variant) or the additional pair of MODs (wt. or variant) comprise at least one 4-1BBL MOD (wt. or variant) polypeptide sequence.
The unconjugated TMAPP or unconjugated duplex TMAPP of any preceding claim, comprising an epitope covalently bound directly, or indirectly through a linker, to the chemical conjugation site to form a TMAPP-epitope conjugate or duplex TMAPP-epitope conjugate.
Dependencies are inferred from the claim text.