Anti-CD8 antibodies, radiolabeled anti-CD8 antibodies, fluorescently labeled anti-CD8 antibodies and their use in imaging are provided herein. Included are methods of detecting the presence of CD8 proteins in a subject or sample.

The present invention relates, in part, to pegylated chimeric proteins comprising one or more targeting moieties, linkers, and one or more signaling moieties, or variants thereof, and their use as therapeutic agents.

Fusion polypeptides including at least one Fc binding domain linked to at least one integrin binding domain are provided. In some embodiments, the at least one Fc binding domain is one or more Fc binding domains from Protein A, Protein G, or Protein Z and the at least one integrin binding domain comprises one or more fibronectin type III domains (for example repeats 12-14 of fibronectin type III domains and optionally the connecting segment of fibronectin). Protein complexes including the polypeptide and one or more antibodies are also provided. Methods of using the polypeptide and/or polypeptide:antibody complex are provided, including treating a subject with a tumor, inducing an immune response to a tumor, and/or targeting an antibody to a tumor cell.

Described is the sequential administration of first a Treg depleting antibody mole-cute selected from antibody molecules, such as an antibody molecule binding specifically to target belonging to the tumour necrosis factor receptor superfamily (TNFRSF), such as a Treg depleting anti-4-1 BB antibody or a Treg depleting OX-40 antibody, and then an immunostimulatory antibody molecule, such as an immunostimulatory anti-4-1 BB anti-body or an immunostimulatory OX-40 antibody, for use in the treatment of cancer. De-scribed are also novel anti-4-1 BB antibodies and novel OX-40 antibodies that may be used in such sequential administration.

Disclosed herein is a personalized tumor vaccine comprising attenuated cancer cells and a method of using said personalized tumor vaccine to treat cancer.

An object of the present invention is to provide a method of treating cancer using a checkpoint inhibitor in combination with REIC/Dkk-3 gene. The present invention is a combination pharmaceutical kit for treating cancer comprising REIC/Dkk-3 in combination with a check point inhibitor and a method for treating cancer by administering REIC/Dkk-3 gene and a check point inhibitor to a cancer patient.

Provided herein are trispecific antibodies that include a) a first monomer, b) a second monomer, and c) a light chain. The first monomer includes a first variant Fc domain and a variable heavy domain, the second monomer includes a second variant Fc domain and a first scFv domain and the light chain includes a variable light domain. The variable heavy domain and the variable light domain form an antigen binding domain. The trispecific antibody further includes a second scFv domain on either the first or second monomers.

Provided are inhibitors of diacylglycerol kinases (DGK) and methods for treating diseases that would benefit from the stimulation of the immune system, such as cancer and infections diseases, comprising administering a DGK inhibitor in combination with an antagonist of the PD 1/PD-L 1 axis and/or an antagonist of CTLA4.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fused to a cell targeting domain and fused to a functional domain. The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and/or vaccination.

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment and tolerance.