Engineered immunostimulatory bacterial strains and uses thereof
US11779612B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jul 23, 2019 |
| Grant date | Oct 10, 2023 |
| Priority date | — |
| Expiry date | Jul 23, 2039 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY02A50/30
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella or modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin− and/or pagP−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd−, purI− and msbB−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment or tumor-resident immune cells and/or induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by admi…
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