Human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2Rβ receptor as compared to wild-type IL-2 for use in combination therapies with anti-PD-1 antibodies for the treatment of cancer. Also provided are pharmaceutical compositions that include such anti-PD-1 antibodies and the disclosed IL-2 muteins.

Provided herein is a conditionally-replicating serotype 5 adenovirus or adenoviral vector expressing a mutant E1A protein under control of a promoter that is responsive to hypoxia and inflammation and one or more immune modulators under control of a tumor-specific promoter. The adenovirus or adenoviral vector also comprises serotype 3 fiber and hexon proteins. Also provided is a method of inducing cytotoxicity in tumor cells using a composition containing the adenovirus or adenoviral vector.

Methods of assembling modified adenoviruses, libraries of adenoviral gene modules and compositions thereof are provided herein.

Provided herein are compositions and methods related to the treatment of an autoimmune disease in a subject.

AAV vectors expressing anti-influenza antibodies are provided. Also described are pharmaceutical compositions useful in delivery same for prophylactic or anti-viral purposes. Methods of delivering such vectors are provided.

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

Methods of inducing an immune response against human immunodeficiency virus (HIV) are described. In particular, methods of inducing an immune response against HIV by co-locally administering an immunogenically effective amount of an isolated HIV envelope (Env) polypeptide and an immunogenically effective amount of an adenovirus vector encoding an HIV antigen, e.g., Env antigen are described. The isolated HIV Env polypeptide and adenovirus vector can be administered in a single composition or in separate compositions, in which the composition or compositions do not contain an adjuvant.

Provided herein are compositions and methods for treating and preventing hearing loss, for treating and preventing a disorder associated with loss, damage, or absence of sensory auditory hair cells, and/or for improving auditory function in a subject in need thereof. Also provided are compositions and methods for the generation of auditory hair cells that allow perception of stimuli in a subject in need thereof.

Contemplated cancer therapies comprise co-administration of aldoxorubicin with an immune therapeutic composition that preferably comprises a vaccine component and a cytotoxic cell component.

The present invention relates to a novel gene delivery system and recombinant adenovirus including the relaxin-encoding sequence to enhance transduction efficiency of transgenes, a pharmaceutical anti-tumor composition including the recombinant adenovirus, a pharmaceutical composition having improved tissue penetration potency and a pharmaceutical composition for treating a disease or disorder associated with accumulation of excess extracellular matrix.