Abstract: PD1-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a PD1 variant or a 4-1BBL variant. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-4-1BBL fusion protein or the isolated polypeptide, host-cells expressing the same and methods of use thereof.

Abstract: LILRB polypeptides are provided. Accordingly, there is provided a LILRB polypeptide capable of binding an HLA-G polypeptide as set forth in SEQ ID NO: 3 and having at least one mutation located within amino acid positions 40-60 of a D1 domain of LILRB, wherein the LILRB polypeptide has an increased stability and/or increased affinity to HLA-G compared to a LILRB polypeptide of the same length and sequence not comprising the at least one mutation. Also provided are polynucleotides encoding the LILRB polypeptide, host cells expressing the LILRB polypeptide and methods of producing and using same.

Abstract: SIRPalpha-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a SIRPalpha variant. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-41BBL fusion protein or the isolated polypeptide, host-cells expressing same and methods of use thereof.

Abstract: SIRPalpha-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a SIRPalpha variant. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-41BBL fusion protein or the isolated polypeptide, host-cells expressing same and methods of use thereof.

Abstract: SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Abstract: Type I membrane proteins heterodimers are provided. Accordingly, there is provided a heterodimer comprising two polypeptides selected from the group consisting of SIRPalpha, PD1, TIGIT, LILRB2 and SIGLEC10, wherein each of the two polypeptides is capable of binding a natural binding pair thereof, and wherein the heterodimer does not comprise an amino acid sequence of a type II membrane protein capable of binding a natural binding pair thereof. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof.

Abstract: SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Abstract: PD1-41BBL fusion proteins are provided. Accordingly, there is provided a PD1-41BBL fusion protein comprising a single amino acid linker between the PD1 and the 41BBL. Also there is provided a PD1-41BBL fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-41BBL fusion protein, host-cells expressing the PD1-41BBL fusion protein and methods of use thereof.

Abstract: PD1-41BBL fusion proteins are provided. Accordingly, there is provided a PD1-41BBL fusion protein comprising a single amino acid linker between the PD1 and the 41BBL. Also there is provided a PD1-41BBL fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-41BBL fusion protein, host-cells expressing the PD1-41BBL fusion protein and methods of use thereof.

Abstract: PD1-CD70 fusion proteins are provided. Accordingly, there is provided a PD1-CD70 fusion protein comprising a single amino acid linker between the PD1 and the CD70. Also there is provided a PD1-CD70 fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-CD70 fusion protein, host-cells expressing the PD1-CD70 fusion protein and methods of use thereof.

Abstract: Methods of culturing T cells with a 4-1BBL fusion polypeptide are provided. Accordingly there is provided a method of culturing T cells comprising adding to immune cells comprising T cells obtained from a subject having a pathology a PD1-4-1BBL or a SIRPalpha-4-1BBL fusion polypeptide; and culturing the immune cells with the fusion polypeptide for more than 7 days. Also provided are T cells obtainable by the method and uses thereof.

Abstract: Methods of culturing T cells are provided. Accordingly there is provided a method of culturing T cells comprising adding to immune cells comprising T cells obtained from a subject having a pathology a non-cellular agent capable of binding 4-1BB and activating said 4-1BB signaling pathway; and culturing the immune cells with said agent for more than 7 days. Also provided are T cells obtainable by the method and uses thereof.

Abstract: PD1-CD70 fusion proteins are provided. Accordingly, there is provided a PD1-CD70 fusion protein comprising a single amino acid linker between the PD1 and the CD70. Also there is provided a PD1-CD70 fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-CD70 fusion protein, host-cells expressing the PD1-CD70 fusion protein and methods of use thereof.

Abstract: Heterodimers are provided. Accordingly, there is provided a heterodimer comprising a dimerizing moiety attached to at least one amino acid sequence of at least one type I membrane protein capable of at least binding a natural ligand or receptor of said at least one type I membrane protein and to at least one amino acid sequence of at least one type II membrane protein capable of at least binding a natural ligand or receptor of said at least one type II membrane protein. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof.

Abstract: SIRPalpha-CD70 fusion proteins are provided. Accordingly, there is provided a SIRPalpha-CD70 fusion protein comprising a single amino acid linker between the SIRPalpha and the CD70. Also there is provided a SIRPalpha-CD70 fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-CD70 fusion protein, host-cells expressing the SIRPalpha-CD70 fusion protein and methods of use thereof.

Abstract: SIRPalpha-CD70 fusion proteins are provided. Accordingly, there is provided a SIRPalpha-CD70 fusion protein comprising a single amino acid linker between the SIRPalpha and the CD70. Also there is provided a SIRPalpha-CD70 fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-CD70 fusion protein, host-cells expressing the SIRPalpha-CD70 fusion protein and methods of use thereof.

Abstract: SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Abstract: SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

Abstract: PD1-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a PD1 variant or a 4-1BBL variant. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-4-1BBL fusion protein or the isolated polypeptide, host-cells expressing the same and methods of use thereof.

Abstract: SIRPalpha-4-1BBL variant fusion proteins are provided. Also provided are isolated polypeptides comprising a SIRPalpha variant. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-41BBL fusion protein or the isolated polypeptide, host-cells expressing same and methods of use thereof.