The disclosure provides modified NK cells and pharmaceutical compositions comrpsing the same. The disclosure also provides methods of treating cancer using the same.

The present invention relates to a heterodimeric Fc-fused protein comprising a first Fc region and a second Fc region of an immunoglobulin Fc pair and a physiologically active protein composed of two or more different subunits, wherein one or more subunits of the physiologically active protein are linked separately to one or more ends of the N-terminus or C-terminus of the first Fc region and/or the second Fc region, and CH3 domains of the first Fc region and the second Fc region are mutated so as to promote the heterodimeric Fc formation. Moreover, the present invention relates to a pharmaceutical composition comprising the heterodimeric Fc-fused protein. The heterodimeric Fc-fused protein according to the present invention has an advantage in that it can retain the activity of a naturally occurring physiologically active protein whose two or more different subunits exhibit physiological activity by forming a protein complex, because the physiologically active protein can be linked to an immunoglobulin heterodimeric Fc such that the naturally occurring form and structure of the fused protein thereof can be maintained. When the heterodimeric Fc-fused protein according to the present invention is used, there is an advantage in that the in vivo half-life of the physiologically active protein contained in the heterodimeric Fc-fused protein can be significantly increased due to the Fc-mediated long half-life such that various physiological activities thereof in vivo can be long-lasting.

The invention relates to an anti-CD16A antigen binding protein for use in NK cell-based immunotherapy, wherein the anti-CD16A antigen binding protein is to be administered intermittently and in combination with a cytokine. In certain embodiments the antigen binding protein is a tetravalent and bispecific CD30/CD16A tandem diabody.

Provided is a cytokine combination for treating a tumor and/or preventing recurrence or metastasis of the tumor. The cytokine combination comprising at least three cytokines selected from the following groups: IL(interleukin)12 or a functional variant thereof, GMCSF (granulocyte-macrophage colony-stimulating factor) or a functional variant thereof, FLT3L (FMS-like tyrosine kinase 3 ligand) or a functional variant thereof, IL2 or a functional variant thereof, IL15 or a functional variant thereof, IL21 or a functional variant thereof, and IL7 or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and/or preventing recurrence or metastasis of the tumor.

Provided in the present invention are a specific antibody of BCMA and a BCMA-targeting immune effector cell, and also provided are a chimeric antigen receptor-modified T cell prepared using the antibody and the use thereof.

The present disclosure concerns combination therapy for cancer thatutilizes (i) an oncolytic virus; (ii) a virus comprising nucleic acid encoding an immunomodulatory factor; and (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen. In particular embodiments, the virus comprises nucleic acid encoding an immunomodulatory factor comprises nucleic acid encoding IL-12 and/or antagonist anti-PD-L1 antibody.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

The present invention provides a chimeric antigen receptor (CAR), comprising an extracellular part, at least one intracellular signaling domain, and at least one transmembrane domain, wherein the extracellular part of said CAR comprises a) at least one antigen binding domain, and b) at least one cytokine receptor activating or blocking domain. The invention also provides isolated nucleic acid molecule(s) encoding for the said CAR, a cell comprising said nucleic acid molecule(s), a cell expressing said CAR and therapeutic uses of said CAR.

The present disclosure provides surprisingly useful fusion polypeptides including an immunomodulatory moiety and a metal-hydroxide binding moiety, as well as various related technologies, including methods of making and of using such fusion polypeptides.

Disclosed herein is an oncolytic recombinant Maraba virus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof. A method for treating a cancer in a patient using the oncolytic recombinant Maraba virus is also disclosed. The present disclosure also provides a tumour cell infected with an oncolytic rhabdovirus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof, for use as an infected cell vaccine (ICV) for the treatment of a cancer. A method for treating a cancer in a patient using the infected cell vaccine is also disclosed.