The invention provides isolated achromosomal dynamic active systems (ADAS), including highly active ADAS. These ADAS provided by the invention can be obtained by a variety of means. Various associated methods of making and using these ADAS are provided.

Disclosed herein is an engineered bacterium comprising a chimeric nucleic acid comprising: a first nucleic acid encoding an ompA protein or a fragment thereof; and a second nucleic acid encoding a radiohapten binding protein. Further disclosed are methods of using these constructs in methods for pre-targeted radiotherapy and for treating tumors.

The present disclosure provides uses of genetically engineered attenuated Salmonella typhimurium strain VNP20009-M in preventing and treating cancer metastasis. The genetically engineered strain VNP20009-M is targeted to cancer cells and has a significant effect of inhibiting metastasis and growth. VNP20009-M can be used to prepare medicaments for the prevention and treatment of tumor metastasis.

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 by 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.sup.. 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.sup., purI.sup., and msbB.sup.. 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 are modified to 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 administering the immunostimulatory bacteria.

The present disclosure relates to a recombinant expression vector for secretion of a VC1 protein and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising an flgM gene, a VC1 gene, and an flhDC gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.

The present disclosure relates to a recombinant expression vector for secretion of chlorotoxin and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising a flgM gene and a chlorotoxin gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.

The present invention relates to a gene construct characterized by encoding a fusion protein of flgM and Strep-tag through the linkage of an anti-sigma factor flgM gene and a gene encoding Strep-tag, enabling the expression of Strep-tag on the surface of an anti-cancer strain that can target tumor sites and stimulate immune activity, and to an anti-cancer adjuvant and tumor imaging agent that, when transformed by this construct, exhibits anti-cancer activity itself and can be effectively utilized in the diagnosis and treatment of tumor cells together with anti-cancer substances or contrast agents labeled with substances specifically interacting with Strep-tag.

A vaccine is disclosed which comprises a pharmaceutically acceptable carrier and Gramnegative bacteria, genetically modified to express: at least one disease-associated antigen, linked to a signal sequence belonging to a type II secretion system; and the at least one disease-associated antigen linked to a signal sequence belonging to a type III secretion system. Uses thereof are also disclosed.

Provided are immunostimulatory bacteria and pharmaceutical compositions containing the bacteria. The immunostimulatory bacteria provided herein contain one or more modalities that enhance the anti-tumor activity of the immunostimulatory bacteria. Among the immunostimulatory bacteria provided are bacteria, such as Salmonella species, which are modified to be auxotrophic or are auxotrophic for adenosine and/or contain plasmids encoding RNAi, such as shRNA and microRNA, that mediate gene disruption and/or expression of immune checkpoints, such as TREX1, VISTA, PD-L1 and, genes that influence the immune system. The bacteria contain additional modifications to enhance their anti-tumor activity. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the pharmaceutical compositions.

The present disclosure relates to a recombinant expression vector for secretion of interleukin-21 and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising an flgM gene and an interleukin-21 gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.