Neospora for use in treating cancer and infectious diseases
Inventors
Dimier-Poisson, Isabelle • MEVELEC, Marie-Noëlle • Ducournau, Céline • MOIRE, Nathalie • MCCRAE, Richard
Assignees
Kymeris Therapeutics Inc • Universite de Tours • Institut National de Recherche pour lAgriculture lAlimentation et lEnvironnement
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Publication Number
US-10736947-B2
Publication Date
2020-08-11
Expiration Date
Abstract
The present invention relates to a strain of Neospora caninum for use in treating cancer or infectious diseases.
Core Innovation
The invention relates to a method for reducing a tumor size in a subject in need thereof by administering a therapeutically effective amount of at least one strain of Neospora caninum at a tachyzoite stage. The disclosed approach suppresses or regresses established solid tumor growth and increases tumor volume decrease in a mouse context. The administration is associated with induction of strong cellular and humoral immune responses.
Neospora caninum strains used in the method include wild-type and mutant strains defined by altered expression of GRA15 and/or ROP16. Mutant strains include GRA15 over-expression and/or ROP16 under-expression, including an ROP16 knockout mutant. The disclosed mutant strain characteristics are stated through validation of GRA15II expression.
The disclosed immune response includes increased IFNγ and increased anti-Neospora specific IgG after Neospora administration. The disclosed content also encompasses formulations and vaccine compositions comprising at least one Neospora caninum strain at a tachyzoite stage, with optional adjuvant, and administration routes including subcutaneous, intradermal, and intratumoral.
Claims Coverage
The independent claim provides a tumor-size reduction method using a therapeutically effective amount of at least one Neospora caninum strain at a tachyzoite stage. Dependent claims introduce inventive features through selection of mutant strain characteristics, quantitative dosing constraints, and narrowing of administration route, tumor types, and formulation/vaccine context with optional adjuvant.
Reducing tumor size with Neospora caninum tachyzoites
A method for reducing a tumor size in a subject in need thereof by administering to the subject a therapeutically effective amount of at least one strain of Neospora caninum, wherein the strain is at a tachyzoite stage.
Neospora caninum tachyzoite-stage dose range in cells
Administering a therapeutically effective amount of at least one Neospora caninum strain at a tachyzoite stage at a cell-count range of about 10^4 to about 10^11.
Mutant strain with altered GRA15 and/or ROP16 expression
Using a Neospora caninum tachyzoite-stage mutant strain characterized by over-expression of GRA15 protein and/or under-expression of ROP16 protein.
Mutant strain includes ROP16 knockout mutant
Using a Neospora caninum tachyzoite-stage mutant strain that comprises an ROP16 knockout mutant.
Route constrained to subcutaneous, intradermal, or intratumoral
Administering at least one Neospora caninum strain at a tachyzoite stage to the subject by subcutaneous administration, intradermal administration, or intratumoral administration.
Target tumor types constrained to ovarian, pancreatic, or melanoma
Wherein the tumor is ovarian cancer, pancreatic cancer, or melanoma.
Vaccine composition including adjuvant
Using at least one Neospora caninum strain at a tachyzoite stage as part of a vaccine composition further comprising an adjuvant.
Across the independent and dependent claim set, the core coverage is tumor-size reduction by administering tachyzoite-stage Neospora caninum, with refinements including a defined cell-count dose range, mutant strain features based on GRA15 and/or ROP16 expression including ROP16 knockout, constrained administration routes, narrowed tumor types, and formulation as a vaccine composition optionally comprising an adjuvant.
Stated Advantages
Suppressing or regressing established solid tumor growth.
Inducing strong cellular and humoral immune responses, including increased IFNγ and increased anti-Neospora specific IgG.
Documented Applications
Reducing a tumor size in a subject, including in solid tumors such as ovarian cancer, pancreatic cancer, and melanoma.
Treatment of chronic infectious diseases described as including immunodepleting or immunosuppressing infections such as HIV, tuberculosis, and malaria.
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