Immunomodulatory minicells and methods of use
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10561719-B2
Publication Date
2020-02-18
Expiration Date
Abstract
The present disclosure is related to immunomodulatory bacterial minicells and methods of using the minicells.
Core Innovation
The invention relates to immunomodulatory bacterial minicells for anticancer therapy. It provides a bacterial minicell comprising perfringolysin O, wherein the minicell is capable of exerting an immunomodulatory anti-tumor effect following administration to a subject.
The invention addresses anticancer treatment that needs anti-tumor immune effects while avoiding toxicity associated with live bacteria. Engineering and safety features in bacterial minicells are used to reduce toxicity compared to live bacteria, while maintaining immunomodulatory and anti-tumor effects.
The minicells may include Th1 cytokines selected from IL-2, GMCSF, IL-12p40, IL-12p70, IL-18, TNF-α, and IFN-γ. Optional invasin targeting, including Yersinia pseudotuberculosis invasin, and additional cargo such as protein toxins are described together with formulation and purity considerations for compositions.
Claims Coverage
The independent claim defines one inventive feature: a perfringolysin O bacterial minicell that exerts an immunomodulatory anti-tumor effect after administration. Dependent claims add optional inventive features for cytokine selection, invasin targeting, and composition constraints.
Perfringolysin O bacterial minicell for immunomodulatory anti-tumor effect
A bacterial minicell comprising perfringolysin O, wherein the minicell is capable of exerting an immunomodulatory anti-tumor effect following administration to a subject.
Th1 cytokine selection in the minicell composition
The minicell further specifies that the Th1 cytokine is selected from IL-2, GMCSF, IL-12p40, IL-12p70, IL-18, TNF-α, or IFN-γ.
Invasin targeting via Yersinia pseudotuberculosis invasin
The bacterial minicell further comprises invasin wherein the invasin is the Yersinia pseudotuberculosis invasin.
Purity constraint on contamination of minicell-producing viable parental cells
The composition includes minicell-producing viable parental cell contamination of less than 1 in 10^5 minicells.
Dry or liquid formulation state of the composition
The composition is formulated as a dry or liquid composition.
Liquid pharmaceutical composition for parenteral administration
The pharmaceutical composition is formulated as a liquid composition for parenteral administration.
Overall, the claim set covers a perfringolysin O bacterial minicell with immunomodulatory anti-tumor effect upon administration, with dependent coverage for Th1 cytokines, Yersinia pseudotuberculosis invasin, and formulation or purity constraints.
Stated Advantages
Exerts an immunomodulatory anti-tumor effect following administration to a subject.
Documented Applications
Anticancer therapy using immunomodulatory bacterial minicells comprising perfringolysin O to exert immunomodulatory anti-tumor effects in immune-competent models.
Anti-tumor effects in metastasis models despite lack of ovarian localization.
Intravesical treatment efficacy in a mouse non-muscle invasive bladder cancer model.
Immunomodulatory anti-tumor activity is lost in severely immune-compromised mice.
Interested in licensing this patent?