Therion Biologics Corporation

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Other

The United States of America As Represented by the Secretary of

The United States of America As Represented by the Department of Health

Dana-farber-cancer Institute Inc.

Sanofi Pasteur Inc.

Theriod Biologics, Incorporated

Dennis L Panicali

Linda R Gritz

Gail P Mazzara

Jeffrey Schlom

Bryan E Roberts

Virginia Stallard

James W Hodge

Anna Mahr

Kwong-Yok Tsang

Steven A Rosenberg

Donald W Kufe

James Tartaglia

Judith A Kantor

Mark Parrington

Neil L Berinstein

Patricia Greenhalgh

Ren&eacute; Bernards

Lawrence K Cohen

Anna Mahe

Antonia T Destree

Erik Kass

The present invention is directed to a system for treating individuals at risk of or suffering from breast cancer. The system comprises administering to the individual a recombinant poxvirus, where the poxvirus contains in a foreign nucleic acid encoding at least one breast cancer antigen.

System for treating and preventing breast cancer

The present invention relates to peptides, polypeptides, and nucleic acids and the use of the peptide, polypeptide or nucleic acid in preventing and/or treating cancer. In particular, the invention relates to peptides and nucleic acid sequences encoding such peptides for use in diagnosing, treating, or preventing melanoma.

Multi-antigen vectors of melanoma

The present invention is directed to a system for treating individuals at risk of developing or suffering from pancreatic cancer. The system comprises administering to the individual a recombinant poxvirus, where the poxvirus contains a foreign nucleic acid encoding at least one pancreatic tumor associated antigen (PTAA).

Custom vectors for treating and preventing pancreatic cancer

The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of these costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater than the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4and CD8T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced antigen-presenting functions.

Recombinant vector expressing multiple costimulatory molecules and uses thereof

The present invention provides novel insertion sites for introducing DNA into pox vectors.

Insertion sites in fowlpox vectors

We have discovered that by using a recombinant viral vector, preferably a pox virus vector having at least one insertion site containing a DNA segment encoding prostate-specific antigen (PSA), operably linked to a promoter capable of expression in the host, a specific humoral and cellular immune response to PSA can be generated. The method preferably comprises introducing a sufficient amount of the recombinant pox virus vector into a host to stimulate the immune response, and contacting the host with additional PSA at periodic intervals thereafter. The additional PSA may be added by using a second pox virus vector from a different pox genus. In another embodiment, additional PSA can be added by contacting the host with PSA by a variety of other methods, including in one preferred embodiment adding PSA. The PSA may be formulated with an adjuvant or in a liposomal formulation.

Generation of immune response to prostate-specific antigen (PSA)

Recombinant pox viruses capable of expressing cell-encoded, tumor-associated antigens are disclosed. The recombinant viruses are useful for evoking an immune response against the antigen.

Recombinant pox virus for immunization against tumor-associated antigens

Recombinant pox viruses capable of expressing an immunogenic fragment of the MUC1 tumor-associated antigen are disclosed. The recombinant viruses can be used as vaccines to prevent the establishment of or treat tumors or pre-tumorous cells expressing the MUC1 tumor-associated antigen. The vaccines can be provided as an admixture comprising: (1) a recombinant pox virus encoding the immunogenic fragment of the MUC1 tumor-associated antigen, and (2) a recombinant pox virus encoding a T-cell co-stimulatory factor. The vaccine admixture can be used, e.g., to prevent establishment of tumors or pre-tumorous cells expressing the MUC1 tumor-associated antigen. The MUC1 specific cytotoxic T-cells can be isolated and expanded and used in a method for treating a host having a tumor expressing MCU1 positive tumor cells.

Recombinant pox virus for immunization against MUC1 tumor-associated antigen

The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4and CD8T cells. The recombinant vectors of the present invention are useful as immunogenes and vaccines against cancer and pathogenic micro-organisms, and in providing host cells, including dendritic cells and splenocytes with enhanced and antigen-presenting functions.

We have discovered that by using a recombinant DNA viral vector, preferably a pox virus vector having at least one insertion site containing a DNA segment encoding the carcinoma self-associated antigen, or a cytotoxic T-cell eliciting epitope thereof, operably linked to a promoter capable of expression in the host, human cytotoxic T-cells specific for the carcinoma self-associated antigens can be produced. The method preferably comprises introducing a sufficient amount of the recombinant pox virus vector into a host to stimulate production of cytotoxic T-cells, and contacting the host with additional antigen at periodic intervals thereafter. The additional antigen may be added by using a second pox virus vector from a different pox genus. In another embodiment, additional antigen is added by contacting the host with antigen. The antigen may be formulated with an adjuvant or in a liposomal formulation. The T-cells can be isolated. The number of T-cells can be expanded by contacting the isolated cytotoxic T-cells alternately with the carcinoma self-associated antigen or an epitope thereof and IL-2. The isolated T-cells can be used in a method for treating a host having a tumor expressing a carcinoma self-associated antigen comprising introducing cytotoxic T-cells specific for the antigen to the host and at at least one periodic interval thereafter introducing to the host a T-cell eliciting epitope of the carcinoma self-associated antigen.

Generation of human cytotoxic T-cells specific for carcinoma self-associated antigens and uses thereof

Generation of immune responses to prostate-specific antigen (PSA)

Recombinant viral vectors which coexpress heterologous polypeptides capable of assembling into defective nonself-propagating viral particles are disclosed. The viral vectors as well as the viral particles can be used as immunogens and for targeted delivery of heterologous gene products and drugs.

Growing community of inventors

Acton, MA, United States of America

Dennis L Panicali