Therapeutic compositions and methods for antibody and Fc-containing targeting molecule-based targeted delivery of bioactive molecules by bacterial minicells

Inventors

Giacalone, Matthew J. • Newman, Michael J.

Assignees

Vaxiion Therapeutics LLC

Abstract

The present application relates to the use of bacterial minicells as targeted delivery agents in vivo and in vitro. Described herein are genetically engineered eubacterial minicells designed to preferentially target and deliver therapeutically relevant agents using a minicell surface coupling molecule capable of binding and displaying antibodies or other Fc-containing targeting moiety fusions and conjugates.

Core Innovation

The invention relates to engineered bacterial minicells and compositions comprising bacterial minicells for treating cancer in a subject, and for targeted delivery and imaging/vaccine purposes. The minicells comprise an Fc-binding fusion protein displayed on their surface and bioactive molecules together with one or more Fc-containing targeting molecules bound to the Fc-binding portion.

The Fc-binding fusion protein includes an outer membrane anchoring domain and an Fc-binding portion of Protein A, wherein the Protein A Fc-binding portion has no F(ab')2 binding capability and comprises no cleavage sites by OmpT protease. Exogenous Fc-containing targeting molecules, such as antibodies, are bound non-covalently to the Fc-binding portion so that Fc regions are masked and the antibody binding sites are presented for recognition of eukaryotic antigens.

The disclosed minicells provide targeting competence toward eukaryotic cell surface molecules, including tumor cell surface molecules, endothelial cell surface molecules, and antigens on professional antigen-presenting cells such as dendritic cells and macrophages. The document also describes genetic minicell production features that make minicell phenotype inducible, including minicell formation via inducible overexpression or mutation of cell-division/chromosome-segregation genes, elimination of viable parent cells using a genetic suicide system with chromosomally integrated recognition sites for inducible homing endonucleases, and additional engineering such as impaired DNA damage repair, ribonuclease III to extend siRNA/shRNA half-life, and expression of cLLO.

Claims Coverage

The relevant independent claim set centers on one cancer-treatment method using Fc-binding bacterial minicells that display a Protein A Fc-binding surface fusion with specified functional limitations, together with bioactive molecules and Fc-containing targeting molecules that recognize a eukaryotic antigen.

The claim coverage centers on administering Fc-binding bacterial minicells for cancer treatment, where surface display of a Protein A Fc-binding fusion with no F(ab')2 binding capability and no OmpT cleavage sites enables binding of Fc-containing targeting molecules that recognize a eukaryotic antigen, alongside bioactive molecules.

Stated Advantages

Documented Applications