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US 11,633,435 B1Granted
Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity
OwnerDavid Gordon Bermudesinventor
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Abstract
Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 antagonists and/or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat of neoplastic diseases including solid tumors and lymphomas.
Claims18
A synthetic genetic construct system, comprising:
- at least two biosynthesis enzyme genes defining at least two different enzymes for production of at least two distinct monomer sugar units, under control of at least two different promoters;
- and
- at least one sugar polymerase gene defining at least one polymerase for polymerization of the at least two distinct monomer sugar units into an antigenic high molecular weight chain comprising an O-antigen polysaccharide,
- wherein an antigenic profile of the antigenic high molecular weight chain comprising the polysaccharide is dependent on independent action of the at least two different promoters, and
- wherein the at least one first biosynthesis gene and the at least one second biosynthesis gene are each part of a rfb gene cluster, and the at least one polymerase gene is an rfc gene, and an antigenic profile of the antigenic high molecular weight chain comprising a polysaccharide is dependent on the at least two different promoters.
2 more elements
A synthetic genetic construct system, comprising:
- at least one first biosynthesis gene controlling production of a first monomer sugar unit having an associated first inducible promoter;
- at least one second biosynthesis gene controlling production of a second monomer sugar unit having an associated second inducible promoter, the first inducible promoter and the second inducible promoter being respectively inducible by different promoters;
- and
- at least one polymerase gene defining at least one polymerase enzyme for polymerization of monomer sugar units into an antigenic high molecular weight chain comprising an O-antigen polysaccharide,
- wherein the at least one first biosynthesis gene and the at least one second biosynthesis gene are each part of a rfb gene cluster, and the at least one polymerase gene is an rfc gene and an antigenic profile of the antigenic high molecular weight chain comprising a polysaccharide is dependent on the at least two different promoters.
2 more elements
Dependencies are inferred from the claim text.