Methods and compositions for generating enhanced immune responses using adenovirus vectors that allow for multiple vaccinations in combination with an IL-15 superagonist complex in subjects in need thereof are provided.

The invention concerns a modified oncolytic adenovirus of serotype Ad5; a pharmaceutical composition comprising same; and a method of treating cancer using same wherein said modified adenovirus comprises at least one point mutation(s) in the hexon hypervariable region 7 (HVR7 mutation) to prevent virus binding with coagulation factor 10 (FX); at least one point mutation(s) in the fiber knob region AB loop (KO1 mutation) to prevent virus binding with the coxsackie and adenovirus receptor (CAR); and at least one point mutation(s) in the penton integrin binding motif Arg-Gly-Asp (RGD) to prevent virus binding with α.sub.Vβ.sub.3/α.sub.Vβ.sub.5 integrin.

The invention provides a replication-deficient serotype 28 adenoviral vector characterized by comprising a portion of a serotype 45 adenoviral hexon protein and/or a portion of a serotype 45 fiber protein in place of the endogenous serotype 28 hexon and/or fiber protein.

The present invention relates to: recombinant adenoviruses, which have an excellent ability to be introduced into stem cells and can be easily introduced into stem cells even at a low concentration; stem cells comprising the same; a gene delivery composition; and a pharmaceutical composition. Stem cells into which adenoviruses are introduced, of the present invention, have excellent in vivo survivability and a treatment effect on tumor cells, and, when used as an anticancer drug, do not cause problems with respect to in vivo survival, hepatotoxicity and the like of stem cells so as to be particularly usable for systemic administration, and have an excellent anticancer effect even in small doses, thereby being widely usable as an anticancer drug using adenoviruses.

The present invention relates to: recombinant adenoviruses, which have an excellent ability to be introduced into stem cells and can be easily introduced into stem cells even at a low concentration; stem cells comprising the same; a gene delivery composition; and a pharmaceutical composition. Stem cells into which adenoviruses are introduced, of the present invention, have excellent in vivo survivability and a treatment effect on tumor cells, and, when used as an anticancer drug, do not cause problems with respect to in vivo survival, hepatotoxicity and the like of stem cells so as to be particularly usable for systemic administration, and have an excellent anticancer effect even in small doses, thereby being widely usable as an anticancer drug using adenoviruses.

This invention provides methods and materials for treating cancer. The invention encompasses methods and materials for delivering programmed death-ligand 1 (PD-L1) binding compounds and/or compositions containing one or more monovalent or multivalent programmed death-ligand 1 (PD-L1) binding compounds which are administered to a mammal having cancer to treat the mammal. In some cases, a multivalent PD-L1 binding compound can include two or more programmed cell death protein 1 (PD-1) polypeptides (and/or fragments thereof having the ability to bind PD-L1). This invention also provides methods and materials for making multivalent PD-L1 binding compounds and methods and materials for making nucleic acid molecules that encode PD-L1 binding compounds.

A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Methods and compositions for generating enhanced immune responses using adenovirus vectors that allow for multiple vaccinations in combination with an IL-15 superagonist complex in subjects in need thereof are provided.

This invention relates to methods and materials for nucleic acid delivery, vaccination, and/or treating cancer. More specifically, methods and materials for nucleic acid delivery, vaccination, and/or treating cancer using one or more recombinant adenoviruses (Ads) as an oncolytic agent are provided.

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.