Vaccine delivery systems using yeast cell wall particles
Inventors
Wagner, Thomas E. • Peoples, Jr., George E.
Assignees
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Publication Number
US-11826476-B2
Publication Date
2023-11-28
Expiration Date
Abstract
The present invention generally relates to compositions and methods for delivering a vaccine. The compositions and methods disclosed herein are particularly useful in making prophylactic and therapeutic vaccines.
Core Innovation
A composition for delivering a vaccine comprises a yeast cell wall particle and a silicate, with exogenous biological material loaded within the yeast cell wall particle. The yeast cell wall particle is modified by coating with the silicate, and the biological material comprises a tumor lysate obtained from a tumor cell line.
The silicate capping is formed using ammonia-mediated silicate capping. The silicate includes orthosilicates such as TEOS and substituted orthosilicates, and the capped particles are described as improving retention and increasing delivery of released biological material into cytoplasm and phagocytic cells versus uncapped particles.
The disclosure also describes vaccine delivery compositions with optional incubation with dendritic cells and immunostimulatory adjuvants. Experimental readouts include in vitro leakage/release and phagocytosis assays, and in vivo mouse survival and lung metastasis comparisons, supporting improved efficacy for tumor lysate-loaded silicate-capped YCWPs used alone or with adjuvants such as CpG and monophosphoryl lipid A.
Claims Coverage
The independent claim defines a vaccine-delivery composition with three core elements: a yeast cell wall particle, a silicate coating, and exogenous biological material loaded within the particle. The dependent claims add selected immunostimulatory adjuvants, optional incubation with an isolated dendritic cell prior to administration, freeze-dried form, and tumor cell line cancer types used to obtain the tumor lysate.
Silicate-coated yeast cell wall particle loaded with tumor lysate
A composition for delivering a vaccine comprising a yeast cell wall particle, a silicate, and an exogenous biological material loaded within the yeast cell wall particle, wherein the yeast cell wall particle is modified by coating with the silicate, and the biological material comprises a tumor lysate obtained from a tumor cell line.
Orthosilicate capping of the coated yeast cell wall particle
The silicate is an orthosilicate in which an organic moiety is attached to each of the four oxygen compounds.
Silicate coating selected from named orthosilicates
The silicate is chosen from tetraethylorthosilicate, tetramethylorthosilicate, tetrapropylorthosilicate, or tetrabutylorthosilicate.
Immunostimulatory adjuvant included as monophosphoryl lipid A or CpG oligonucleotide
An adjuvant is included wherein the adjuvant is either monophosphoryl lipid A or a CpG oligonucleotide.
Optional incubation with an isolated dendritic cell prior to administration
The biological-material-loaded particle is additionally incubated with an isolated dendritic cell before administration.
Tumor lysate obtained from specified tumor cell line cancer types
The tumor lysate is obtained from a tumor cell line selected from breast, small cell lung, non-small cell lung, glioma, medulloblastoma, neuroblastoma, Wilms tumors, rhabdomyosarcoma, osteosarcoma, liver, pancreatic, melanoma, prostate, and ocular melanoma.
Coverage centers on a yeast cell wall particle coated with a silicate and loaded with tumor-lysate exogenous biological material, with further scope defined by orthosilicate structure and identity, optional monophosphoryl lipid A or CpG, optional incubation with an isolated dendritic cell prior to administration, and tumor cell line cancer types used to obtain the tumor lysate.
Stated Advantages
Improves retention.
Increases delivery of released biological material into cytoplasm and phagocytic cells versus uncapped particles.
Improved efficacy supported by in vitro leakage/release and phagocytosis assays and in vivo mouse survival and lung metastasis comparisons.
Documented Applications
Vaccine delivery using yeast cell wall particles loaded with exogenous biological material, including tumor lysate from a tumor cell line.
Tumor-lysate-based vaccine delivery compositions used alone or with immunostimulatory adjuvants including CpG and monophosphoryl lipid A.
Use in compositions optionally incubated with dendritic cells prior to administration.
Evaluation in in vivo mouse survival study and lung metastasis after tumor challenge comparisons.
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