Hydrogel delivery of sting immunotherapy for treatment cancer
Inventors
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Assignees
William Marsh Rice University • University of Texas System
Member
Rice UniversityRice University is a leading research university in Houston, Texas, recognized for its emphasis on scientific discovery, innovation, and interdisciplinary collaboration. The institution is committed to academic excellence, impactful research, and community engagement, offering robust undergraduate and graduate programs in engineering, natural sciences, social sciences, humanities, business, and the arts. Rice is distinguished by its history of collaboration with organizations such as NASA, fostering advances in space science, biotechnology, energy research, and artificial intelligence.
Rice University is a leading research university in Houston, Texas, recognized for its emphasis on scientific discovery, innovation, and interdisciplinary collaboration. The institution is committed to academic excellence, impactful research, and community engagement, offering robust undergraduate and graduate programs in engineering, natural sciences, social sciences, humanities, business, and the arts. Rice is distinguished by its history of collaboration with organizations such as NASA, fostering advances in space science, biotechnology, energy research, and artificial intelligence.
Publication Number
US-11969499-B2
Publication Date
2024-04-30
Expiration Date
Abstract
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.
Core Innovation
The disclosure provides compositions comprising multi domain peptide (MDP) hydrogels and cyclic dinucleotides (CDNs) and methods of using such compositions in the treatment of cancer. In particular, compositions comprising (a) a multi domain peptide (MDP) hydrogel and (b) a cyclic dinucleotide (CDN) are provided, and the MDP hydrogel and the CDN may be covalently or non-covalently bound to each other. The CDN may be a natural endogenous CDN or a synthetic CDN, and examples of CDNs and CDN analogs are disclosed in the specification.
The background identifies limited efficacy of CDN monotherapy in certain cancers, specifically head and neck squamous cell carcinoma (HNSCC), including tumors that are non-T cell inflamed or treatment resistant, and the need for new approaches to improve the efficacy of CDN in challenging, treatment-refractory tumors. The disclosure addresses this problem by combining a CDN STING agonist with an MDP hydrogel delivery platform designed to provide localized, controlled release, recruit antigen presenting cells, and improve anti-tumor immune responses.
Claims Coverage
One independent claim was identified, comprising two main inventive features.
MDP hydrogel K2(SL)6K2 or R2(SL)6R2
A multi-domain peptide (MDP) hydrogel having sequence K2(SL)6K2 (SEQ ID NO: 3) or R2(SL)6R2 (SEQ ID NO: 4) as an element of the composition.
Cyclic dinucleotide (CDN)
A cyclic dinucleotide (CDN) included as an element of the composition.
The independent claim covers a composition that combines a specified MDP hydrogel (K2(SL)6K2 or R2(SL)6R2) together with a cyclic dinucleotide (CDN).
Stated Advantages
Extended and controlled release of CDN from MDP hydrogels compared to collagen control gels.
MDP hydrogels are thixotropic, allowing syringe delivery and localization for intra-tumoral injections.
MDP hydrogels undergo complete cellular infiltration in three days and are not fibrously encapsulated, maximizing matrix-tissue interaction.
MDP hydrogels recruit immune cells, including antigen presenting cells such as dendritic cells, to sites of injection.
STINGel (MDP+CDN) produced superior anti-tumor efficacy in a murine head and neck cancer model, including increased survival and durable immunological memory after a single injection.
MDP hydrogels are well-tolerated in vivo and generate a moderate initial inflammatory response.
Documented Applications
Treatment of cancer using a composition comprising an MDP hydrogel and a CDN, including methods of treating carcinomas, sarcomas, lymphomas, leukemias, melanomas, mesotheliomas, multiple myeloma, and seminoma as listed in the specification.
Treatment of cancers of specified organs and tissues, including but not limited to head and neck cancer, and head and neck squamous cell carcinoma (HNSCC).
Treatment of treatment resistant cancers, primary cancers, recurrent cancers, metastatic cancers and non-T cell inflamed cancers.
Intratumoral administration, administration to the tumor bed, or regional administration to the tumor as routes of delivering the composition.
Use of the composition in combination with a second cancer therapy such as a chemotherapeutic agent, gene therapy, surgery, radiotherapy, or an immunotherapy.
Formulation for multiple routes of administration including oral, topical, and various local or parenteral routes as explicitly listed in the summary.
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