Hydrogel delivery of sting immunotherapy for treatment cancer
In one aspect, the present disclosure provides for novel compositions of matter comprising multi domain peptide (MDP) hydrogels and cyclic dinucleotides (CDNs). Also disclosed are method of using such compositions in the treatment of cancer, including in particular the treatment of head and neck cancers, such as those resistant to CDN therapy.
1. A composition comprising (a) a multi-domain peptide (MDP) hydrogel K 2 (SL) 6 K 2 (SEQ ID NO: 3) or R 2 (SL) 6 R 2 (SEQ ID NO: 4) and (b) a cyclic dinucleotide (CDN).
2. The composition of claim 1 , wherein the CDN is a natural endogenous CDN.
3. The composition of claim 1 , wherein the CDN is a CDN analog comprising a modified base or non-natural internucleoside linkage.
4. The composition of claim 1 , the CDN is dithio-(R P ,R P )-[cyclic[A(2′,5′)pA(3′,5′)p]], 2′2′-cGAMP, 2′3′-cGAMP, 3′3′-cGAMP, c-di-AMP, 2′3′-c-di-AMP, 2′3′-c-di-AM(PS) 2 , c-di-GMP, c-di-UMP, c-di-IMP.
5. The composition of claim 1 , wherein peptides of MDP hydrogel are 18-30 residues in length.
6. The composition of claim 1 , wherein peptides of the MDP hydrogel have about a 3:1 ratio of hydrophilic to hydrophobic charged residues.
7. The composition of claim 1 , wherein the peptides of the MDP hydrogel contain a bio-mimetic sequence.
8. The composition of claim 1 , wherein the MDP hydrogel comprises a degradable sequence containing a tumor specific peptide.
9. The composition of claim 1 , wherein the MDP hydrogel and the CDN are covalently or non-covalently bound to each other.
10. The composition of claim 1 , wherein the endogenous CDN is produced by cGAS.
11. The composition of claim 1 , wherein the CDN is a synthetic CDN.