Abstract: Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.

Abstract: Disclosed are and methods for expanding tumor infiltrating lymphocyte (TIL) populations and methods of the use of the expanded TIL population for treating cancer. In one aspect, disclosed herein are methods of generating tumor infiltrating lymphocytes comprising a) administering an effective amount of an oncolytic virus expressing one or more exogenous immunostimulatory molecules (such as, for example, CD40-L, MEM40, B7-1(CD80)/B7-2(CD86), OX40L, 4-1BBL, CD70, GITRL, LIGHT, TIM-4, ICAM-1, CD58 and/or SLAMF6) into a tumor cell; and b) harvesting the tumor infiltrating lymphocytes. In some aspects, the oncolytic virus can further express one or more type 1 interferon (IFN)(such as, for example, IFN-?, IFN-?, IFN-?, IFN-?, IFN-?, IFN-?, IFN-?, and/or IFN-?). In some aspects, the TILs generated are obtained in the tumor microenvironment at the site of the administration of the oncolytic virus; however TILs can also be obtained at tumor microenvironments not infected with the oncolytic virus.

Abstract: Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

Abstract: The present disclosure provides methods and compositions for enhancing immunity by administering a coronavirus vaccine and a chimeric CD40L polypeptide. The coronavirus vaccine can be comprised of inactivated coronaviral particles or an antigenic polypeptide, preferably the coronavirus spike protein. The coronavirus antigenic polypeptide can be a purified antigenic polypeptide or a nucleic acid expression construct that encodes the antigenic polypeptide. The chimeric CD40L polypeptide in compositions of the invention can be a purified chimeric CD40L polypeptide or a nucleic acid expression construction that encodes the chimeric CD40L polypeptide.

Abstract: The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFN? and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFN? and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

Abstract: Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.

Abstract: Provided herein are methods of sensitizing cancer cells to treatment with inhibitors of the PD-1 pathway. Such methods comprise treatment of subject with a checkpoint inhibitor refractory cancer with an expression vector encoding a chimeric CD154.

Abstract: Disclosed are replication-competent oncolytic adenoviruses, comprising chimeric human/mouse CD40 ligands. The oncolytic adenoviruses may be replication competent. The chimeric human/mouse CD40 ligand may be MEM40. Also disclosed are methods comprising administering a replication competent oncolytic adenovirus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from a cancer.

Abstract: Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF?, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF?, wherein the encoded domain or subdomain replaces a cleavage site of native TNF?, and a second nucleotide sequence encoding a domain or subdomain of native TNF? that binds to a TNF? receptor. The encoded chimeric TNF? is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF? receptor on the surface of a cell. The chimeric TNF? is therefore useful in methods for inducing apoptosis of a cell expressing a TNF? receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF? that is expressed on the surface of the cell.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF?, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF?, wherein the encoded domain or subdomain replaces a cleavage site of native TNF?, and a second nucleotide sequence encoding a domain or subdomain of native TNF? that binds to a TNF? receptor. The encoded chimeric TNF? is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF? receptor on the surface of a cell. The chimeric TNF? is therefore useful in methods for inducing apoptosis of a cell expressing a TNF? receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF? that is expressed on the surface of the cell.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF?, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF?, wherein the encoded domain or subdomain replaces a cleavage site of native TNF?, and a second nucleotide sequence encoding a domain or subdomain of native TNF? that binds to a TNF? receptor. The encoded chimeric TNF? is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF? receptor on the surface of a cell. The chimeric TNF? is therefore useful in methods for inducing apoptosis of a cell expressing a TNF? receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF? that is expressed on the surface of the cell.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF? and chimeric TNF? polypeptides. The former have a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF?, wherein the encoded domain or subdomain lacks a cleavage site, and a second nucleotide sequence encoding a domain or subdomain of native TNF? that binds to a TNF? receptor. The encoded chimeric TNF? is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF? receptor on the surface of a cell. The chimeric TNF? is therefore useful in methods for inducing apoptosis of a cell expressing a TNF? receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF? that is expressed on the surface of the cell.

Abstract: The invention provides a stable lyophilized composition of 5,10 methylenetetrahydrofolate suitable for use in the treatment of cancer and other therapies. The composition comprises 5,10-MTHF in combination with citric acid and ascorbic acid, with the ratio of citric acid to ascorbic acid from about 0.75:1 to about 2.25:1 by weight, and the ratio of total citric acid and ascorbic acid to 5,10-MTHF from about 1.4:1 to about 3.4:1 by weight. Prior to lyophilization, the solution is adjusted to an essentially neutral pH.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Abstract: The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The first nucleotide sequence preferably further encodes an extracellular subdomain of non-human CD154 that is critical for expression of said CD154 by cells, such as human CD40+ cells, and another extracellular domain that detects expression of the chimeric CD154 by binding to anti-murine antibodies. The second nucleotide sequence preferably further encodes an extracellular subdomain of human CD154 to which functionally inhibitory anti-CD154 antibodies bind.