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The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders. Fr-kitt Iys-nplaoma receptor ;: Other anttbotiies dimini4tx CXCR5 sactivi. I 3 is a ligand of C"XClti5 and is expressed constitutively ora strornal cells, srrclr as fOlliCtt[ar det:

Ch1 moda solutions 1

Cholera the medicinal preparation containing antigens or antibodies, e. The microorganisms are designed to accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisms.

The microorganisms also are designed or modified to result in leaky cell membranes of cells in which they accumulate, resulting in production of antibodies reactive against proteins and other cellular products and also permitting exploitation of proferating proliferating tissues, particularly tumors, to produce selected proteins and other products.

Vaccines containing the microorganisms are provided. Combinations of the microorganisms and anti-cancer agents and uses thereof for treating cancer also are provided.

Szalay, Tatyana Timiryasova, Yong A. Yu and Qian Zhang, filed on Jun. This application also is related to International Application Serial No.

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This application also is related to U. In particular, modified bacteria, eukaryotic cells and viruses are provided and methods of use thereof for treatment of proliferative and inflammatory disorders and for production of products in tumors are provided.

One surgeon, William Coley, administered live Streptococcus pyogenes to patients with tumors with limited Ch1 moda solutions 1.


In the early 20th century, scientists documented vaccinia viral oncolysis in mice, which led to administration of several live viruses to patients with tumors from the s through the s. These forays into this avenue of cancer treatment were not successful.

Since that time, a variety of genetically engineered viruses have been tested for treatment of cancers. In one study, for example, nude mice bearing nonmetastatic colon adenocarcinoma cells were systemically injected with a WR strain of vaccinia virus modified by having a vaccinia growth factor deletion and an enhanced green fluorescence protein inserted into the thymidine kinase locus.

The virus was observed to have antitumor effect, including one complete response, despite a lack of exogenous therapeutic genes in the modified virus McCart et al. In another study, vaccinia melanoma oncolysate VMO was injected into sites near melanoma positive lymph nodes in a Phase III clinical trial of melanoma patients.

The melanoma patients treated with VMO had a survival rate better than that for untreated patients, but similar to patients treated with the VV control Kim et al. Other studies have demonstrated limited success with this approach. This therapy is not completely effective, particularly for systemically delivered viruses or bacteria.

Limitations on the control of microbial vehicle function in vivo result in ineffective therapeutic results as well as raising safety concerns.

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It would be desirable to improve this type of therapy or to develop more effective approaches for treatments of neoplastic disease. Therefore, among the objects herein, it is an object to provide therapeutic methods and microorganisms for the treatment of neoplastic and other diseases.

SUMMARY Provided herein are therapeutic methods and microorganisms, including viruses, bacteria and eukaryotic cells, for uses in the methods for the treatment of neoplastic diseases and other diseases.

Such tissues include tumors and other tissues and cells involved in other proliferative disorders, wounds and other tissues involved in inflammatory responses. The microorganisms, which include bacterial cells, viruses and mammallian cells, are selected or are designed to be non-pathogenic and to preferentially accumulate in the immunoprivileged tissues.

The microorganisms, once in the tissues or cells or vicinity thereof, affect the cell membranes of the cells in such tissues so that they become leaky or lyse, but sufficiently slowly so that the targeted cells and tumors leak enough antigen or other proteins for a time sufficient to elicit an immune response.

The microorganisms are administered by any route, including systemic administration, such as i. In exemplary methods, the microorganisms are used to treat tumors and to prevent recurrence and metastatic spread.

Exemplary microorganisms include highly attenuated viruses and bacteria, as well as mammallian cells.

Generic Risks

The microorganisms are optionally modified to deliver other products, including other therapeutic products to the targeted tissues. When the microorganisms are administered to a host that contains tumors, the tumors in the host essentially become antigen and protein factories.

This can be exploited so that the tumors can be used to produce proteins or other cellular products encoded by or produced by the microorganisms. In addition, the host sera can be harvested to isolate antibodies to products produced by the microorganisms as well as the tumor cells.Page 1 CHAPTER 1 HW SOLUTIONS: STRUCTURE FORMAL CHARGE 1.!Indicate the formal charge on any atom that has a non-zero formal charge.

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