Abstract: Modified alphaviruses encoding a SARS-CoV-2 spike protein or antigenic segment of the SARS-CoV-2 spike protein are provided. The modified alphaviruses include replicative defective Sindbis viruses. The modified viruses express or are administered with an immunomodulatory agent that is an agonist antibody or antigenbinding fragment thereof, or a cytokine, or a combination thereof. Pharmaceutical compositions that include the modified alphaviruses and methods of using the modified alphaviruses and compositions that contain them are provided. The compositions are used to stimulate a therapeutic or protective effect against SARS-CoV-2 infection that includes humoral and cell mediated responses.

Abstract: The present disclosure provides compositions and methods for the treatment of cancer. More specifically, the present disclosure provides compositions and methods utilizing a combination of an oncolytic viruses, such as Sindbis virus, and antibodies directed against a co-stimulatory molecule or to an immune system agonist molecule, such as anti-OX40 antibodies and anti-4-1BB antibodies.

Abstract: The subject application is directed to a method for treating a mammal harboring a tumor comprising identifying a tumor associated antigen (TAA) expressed by the tumor and parenterally administering to the mammal a therapeutically effective amount of a Sindbis viral vector carrying a gene encoding the TAA to the mammal sufficient to elicit an immune response directed against the tumor, and thereby treating the tumor.

Abstract: Provided are polynucleotides and viral vectors, particularly, Alphavirus vectors such as Sindbis viral vectors, which encode an immune checkpoint protein, or a ligand binding portion of the checkpoint protein, or an immune checkpoint protein or ligand binding portion thereof fused to one or more immunoglobulin (Ig) domains, e.g., an Ig hinge region and an Ig heavy chain constant domain. Methods of treating a mammalian subject having a cancer or tumor are provided, in which the viral vectors, e.g., a Sindbis virus vector, encoding the immune checkpoint protein, a ligand binding portion thereof, or a checkpoint protein fusion protein as described, are administered to the subject, resulting in an anti-cancer or anti-tumor immune response, significant reduction in tumor growth in the treated subject and increased survivability.

Abstract: Provided are polynucleotides and viral vectors, e.g., alphavins or Sindbis viral vectors, encoding multiple, e.g., two or more, epitopes of at least one tumor associated antigen, in which each epitope is separated by a processing or enzyme cleavage site. The encoded epitopes may be the same or different. Also provided are polynucleotides and viral vectors, particularly, alphavirus or Sindbis viral vectors, encoding an immune checkpoint protein, or a ligand binding portion thereof. The immune checkpoint protein or ligand binding portion thereof may be fused to immunoglobulin domains, e.g., an Ig hinge domain and an Ig heavy chain constant domain. Methods of treating subjects having a cancer or tumor, e.g., a TAA-expressing tumor, with the described viral vectors are provided.

Abstract: The subject application is directed to a method for treating a mammal harboring a tumor comprising identifying a tumor associated antigen (TAA) expressed by the tumor and parenterally administering to the mammal a therapeutically effective amount of a Sindbis viral vector carrying a gene encoding the TAA to the mammal sufficient to elicit an immune response directed against the tumor, and thereby treating the tumor.

Abstract: The subject application is directed to a method for treating a mammal harboring a tumor comprising identifying a tumor associated antigen (TAA) expressed by the tumor and parenterally administering to the mammal a therapeutically effective amount of a Sindbis viral vector carrying a gene encoding the TAA to the mammal sufficient to elicit an immune response directed against the tumor, and thereby treating the tumor.

Abstract: Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.

Abstract: Disclosed herein are methods for treating a mammal harboring a solid tumor which expresses higher levels of High Affinity Laminin Receptors (LAMR) than normal cells of the same lineage comprising systematically administering to a mammal in need of such treatment a therapeutically effective amount of a Replication Competent (RC) Sindbis virus vector, wherein said vector encodes a suicide gene.

Abstract: A method for treating malignant tumors with Sindbis viral based vectors in combination with antitumor agents and pharmaceutical formulations for use in such treatment.

Abstract: The subject application is directed to a method for treating a mammal harboring a tumor comprising identifying a tumor associated antigen (TAA) expressed by the tumor and parenterally administering to the mammal a therapeutically effective amount of a Sindbis viral vector carrying a gene encoding the TAA to the mammal sufficient to elicit an immune response directed against the tumor, and thereby treating the tumor.

Abstract: The present invention pertains to compounds which interfere with the binding of laminin to the laminin receptor (LamR). Such compounds are useful for treating diseases such as cancer, Alzheimer's Disease, and certain viral and bacterial infections.

Abstract: Disclosed herein are new defective Sindbis viral vectors made from wild type Ar-339 Sindbis virus, with differences in replicase and envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are plasmids used for the production of the vectors, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.

Abstract: Disclosed herein are methods for treating a mammal harboring a solid tumor which expresses higher levels of High Affinity Laminin Receptors (LAMR) than normal cells of the same lineage comprising systematically administering to a mammal in need of such treatment a therapeutically effective amount of a Replication Competent (RC) Sindbis virus vector, wherein said vector encodes a suicide gene.

Abstract: A human laminin receptor crystal is disclosed. Methods are disclosed for using various computer and non-computer means in order to develop models for use in the development of novel therapeutics that block and/or mimic laminin receptor interactions in the setting of, among others, Alzheimer's disease, other neurological disorders, cancer, and viral and bacterial infections.

Abstract: Disclosed herein are new defective Sindbis viral vectors made from a novel Helper plasmid, with differences in envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are vectors produced using the plasmid, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.

Abstract: A method for treating malignant tumors with Sindbis viral based vectors in combination with antitumor agents and pharmaceutical formulations for use in such treatment.

Abstract: Disclosed herein are methods for identifying cancer cells and monitoring anti-cancer therapy in the body of a mammal by systemically delivering Sindbis viral vectors. The vector can specifically target and identify tumor cells in mice growing subcutaneously, intraperitoneally, intrapancreatically, or in the lungs. These findings demonstrate the remarkable specificity of the Sindbis vector system that is relatively safe and can specifically target tumor cells throughout the body via the bloodstream.

Abstract: The present invention relates to methods and compositions for treating tumors using vectors that preferentially target tumor cells. In particular, the invention relates to alphavirus-based, preferably Sindbis virus-based, vectors and to non-alphavirus-based vectors, which have a preferential affinity for high affinity laminin receptors (HALR). These vectors are efficiently targeted to tumors and have the ability to cause tumor necrosis.

Abstract: Disclosed herein are new defective Sindbis viral vectors made from a novel Helper plasmid, with differences in envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are vectors produced using the plasmid, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.