Described herein are compositions that include monoclonal antibodies that specifically bind Hsp90α and methods of using the same to treat HIF-1a-overexpressing cancer. In some embodiments, the cancers are breast cancer or lung cancer. The monoclonal antibodies bind the epitope TKPIWTRNP in Hsp90α or VKHFSVEGQ in Hsp90α.

The present disclosure provides anti-nucleolin antibodies, methods of producing anti-nucleolin antibodies, and cells producing anti-nucleolin antibodies. Also provided are methods of using anti-nucleolin antibodies in treating malignant and non-malignant diseases.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

A fusion protein comprising: a first component comprising an antibody, or a fragment or variant thereof; and a second component comprising a cytokine trap or an adenosine deaminase or a fragment or variant thereof. In certain embodiments, the antibody is an anti-PD-1 antibody. In certain embodiments, the antibody binds to a tumor antigen, for example a MUC16 or MUC1 antigen. In certain embodiments, the cytokine trap is a TGF-β trap. A polynucleotide encoding such a fusion protein and a vector comprising such a polynucleotide. A composition comprising the fusion protein. A method of using the composition, including in the treatment of cancer.

Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD11b.sup.+GR1.sup.− (Ly6C−)) monocytes; or CD14.sup.+CD16.sup.+ monocytes and/or CD14.sup.dimCD16.sup.+ (CD115.sup.+CD111b.sup.+GR1.sup.− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

Aspects of the present disclosure are directed to methods and compositions for facilitating β-cell regeneration by inhibition of the HIF1α-PFKFB3 pathway. Certain aspects describe methods for treatment and prevention of prediabetes and diabetes, including type 2 diabetes. Also disclosed are methods and compositions for enhancing β-cell regeneration.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.

Fibronectin type III (.sup.10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative .sup.10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes .sup.10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are .sup.10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.