Newlink Genetics Corporation

Central Iowa Health System

Human Gene Therapy Research Institute

Iowa Health System

Lankeanau Institute for Medical Research

Lankenau Institute for Medical Research

Charles J Link

Gabriela Rossi

Firoz Jaipuri

Mario Mautino

Nicholas N Vahanian

Tatiana Seregina

Won-Bin Young

Sanjeev Kumar

Jesse Waldo

Tanay Kesharwani

George C Prendergast

William Malachowski

John P Levy

Sheldon B Greer

Judith Lalonde

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. The present invention describes prophylactic or therapeutic cancer vaccines based on purified TAA proteins or TAA-derived synthetic peptides altered by chemical, enzymatic or chemo-enzymatic methods to introduce &#x3b1;Gal epitopes or &#x3b1;Gal glycomimetic epitopes, in order to allow for enhanced opsonization of the antigen by natural anti-&#x3b1;Gal antibodies to stimulate TAA capture and presentation, thereby inducing a humoral and cellular immune response to the TAA expressed by a tumor. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

Enhanced immunogenicity of tumor associated antigens by addition of alphagal epitopes

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. Through ex vivo gene therapy protocols tumor cells are engineered to express an &#x3b1;(1,3)galactosyl epitope. The cells are then irradiated or otherwise killed and administered to a patient. The &#x3b1;-galactosyl epitope causes opsonization of the tumor cell enhancing uptake of the opsonized tumor cell by antigen presenting cells which results in enhanced tumor specific antigen presentation. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

Antitumor vaccination using allogeneic tumor cells expressing alpha (1,3)-galactosyltransferase

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. Through ex vivo gene therapy protocols tumor cells are engineered to express an &#x3b1;(1,3)galactosyl epitope. The cells are then irradiated or otherwise killed and administered to a patient. The &#x3b1; galactosyl epitope causes opsonization of the tumor cell enhancing uptake of the opsonized tumor cell by antigen presenting cells which results in enhanced tumor specific antigen presentation. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

Presently provided are compounds according to the formula (I) or (II), and pharmaceutical compositions comprising the compounds, wherein R, R, and Rare defined herein. Such compounds and compositions are useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosuppression associated with an infectious disease. 

IDO inhibitors

Presently provided are compounds according to the formula (I) or (II), and pharmaceutical compositions comprising the compounds, wherein R, R, and Rare defined herein. Such compounds and compositions are useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine -2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease. 

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. Through ex vivo gene therapy protocols tumor cells are engineered to express an &#x3b1; (1,3) galactosyl epitope. The cells are then irradiated or otherwise killed and administered to a patient. The &#x3b1; galactosyl epitope causes opsonization of the tumor cell enhancing uptake of the opsonized tumor cell by antigen presenting cells which results in enhanced tumor specific antigen presentation. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. The present invention describes prophylactic or therapeutic cancer vaccines based on purified TAA proteins or TAA-derived synthetic peptides altered by chemical, enzymatic or chemo-enzymatic methods to introduce &#x3b1;Gal epi topes or &#x3b1;Gal glycomimetic epitopes, in order to allow for enhanced opsonization of the antigen by natural anti-&#x3b1;Gal antibodies to stimulate TAA capture and presentation, thereby inducing a humoral and cellular immune response to the TAA expressed by a tumor. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.

Enhanced immunogenicity of tumor associated antigens by addition of &#x3b1;gal epitopes

Enhanced immunogenicity of tumor associated antigens by addition of alphaGal epitopes

Antitumor vaccination using allogeneic tumor cells expressing alpha (1,3)-galactosyl transferase

A method for treating tumors. Through infusion or xenotransplantation of xenogeneic cells, such as infusion of murine cells into the peritoneal cavity of humans, a hyperacute rejection response to the cells is induced. This in turn creates a bystander effect to the tumor. This effect creates tumor regression. This treatment can be used alone or in conjunction with gene therapy or chemotherapy treatments.

Method for tumor treatment using infusion of xenogeneic cells to induce hyperacute rejection and innocent bystander effect

The present invention pertains to combination radio therapy of tumors and more specifically to pharmaceutical compositions, and methods of treatment by gene therapy designed to sensitize tumors in animals, notably humans, and render them more susceptible to radiation, thus significantly reducing the amount of radiation required to kill neoplastic cells while at the same time making the radiation far more tissue specific to the tumor site.

Radiation enhanced gene therapy for tumors expressing a gene for a viral pyrimidine kinase in the presence of a 5&prime;-halogenated pyrimidine

The invention discloses methods and compositions for killing tumor cells in animals. Through transfer techniques, cancer cells are engineered to express an epitope which is targeted by natural antibodies causing complement destruction of transformed tumor cells that is typically associated with hyperacute xenograft rejection.

Growing community of inventors

Clive, IA, United States of America

Charles J Link