Provided are embodiments of replicative oncolytic adenovirus AD5 ApoA1 for inhibiting tumor growth and metastasis and use thereof in preparation of anti-tumor drugs. The virus can rapidly replicate in tumor cells and exert an oncolytic effect. Tumor cells infected with the virus can highly express apolipoprotein ApoA1 which can be secreted extracellularly in large quantities, significantly inhibit the invasion and metastasis of tumor cells, inhibit tumor-promoting inflammation pathways, and significantly reduce a IDO-1 which is a key molecule that leads to tumor immune escape. The virus can significantly inhibit tumor growth, inhibit tumor invasion, delay progression of cachexia and prolong the survival time of tumor-bearing mice in mice with liver cancer, breast cancer, colon cancer, or lung cancer.

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

Provided is the use of selectively replicating oncolytic viruses in the preparation of immunostimulants for treatment of tumors and/or cancers, wherein the oncolytic viruses do not carry exogenous immunoregulatory genes.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies of humans. More specifically, the present invention relates to an oncolytic adenoviral vector encoding a bispecific monoclonal antibody. Furthermore, the present invention relates to methods and uses utilizing the oncolytic adenoviral vectors, also together with adoptive cell therapies.

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-α, IFN-β, IFN-κ, IFN-δ, IFN-ε, IFN-τ, IFN-ω, and/or IFN-ζ). 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.

The present invention provides methods for treating an individual having bladder cancer comprising intravesically administering to the individual an oncolytic virus. Also provided are pharmaceutical compositions and kits for treating bladder cancer.

The present application provided defective bovine adenovirus (BAV) vectors that lack pV function. Cell lines and methods of preparing such vectors are provided. In addition, the invention provides methods of treating a disease or disorder with a defective BAV lacking pV function as well as vaccine comprising a defective BAV lacking pV function.

The present invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to a use of said vectors in the manufacture of a medicament for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing peptidylarginine deiminase and TIMP in a cell and increasing anti-tumor effect and induction of specific immune response in a subject, as well as uses of the oncolytic adenoviral vector of the invention for producing transgenes in a cell and increasing anti-tumor effect and generation of specific immune response in a subject.

The present invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to a use of said vectors in the manufacture of a medicament for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing B7 family of immune-regulatory ligands and ADA in a cell and increasing anti-tumor effect and induction of specific immune response in a subject, as well as uses of the oncolytic adenoviral vector of the invention for producing transgenes in a cell and increasing anti-tumor effect and generation of specific immune response in a subject.