Method of reducing bispecific t cell engager or chimeric antigen receptor t cell mediated cytokine release syndrome using interleukins-4, -10, or a fusion protein thereof

A method of reducing cytokine release syndrome (CRS) severity induced by using a bispecific antibody or chimeric antigen receptor T cell (CAR-T) during treatment of a malignant disease and enhancement of tumor cytolysis comprising administering to a patient in need thereof

• (a) an amount of a composition comprising a dual cytokine fusion protein of Formula II
• NH2-(Y)-(X1)-(Zn)-(X2)-(Y)-COOH (Formula II)
• wherein
• “Y” is a monomer of IL10 comprising a sequence of SEQ ID No.:
• 5, or a variant thereof;
• “X1” is a VL or VH region from a first monoclonal antibody;
• “X2” is a VH or VL region from the first monoclonal antibody;
• wherein when X1 is a VL, X2 is a VH or when X1 is a VH, X2 is a VL,
• wherein the first monoclonal antibody is an anti-ebola antibody;
• wherein the VL and VH from the anti-ebola antibody include 3 light chain CDRs and 3 heavy chain CDRs that are engrafted with 3 light chain CDRs and 3 heavy chain CDRs from an anti-EGFR monoclonal antibody;
• “Z” is an IL-2;
• and
• “n” is an integer of 1;
• and
• (b) an amount of a bispecific antibody or CAR-T, wherein the bispecific antibody comprises specificity for a CD3 and a tumor associated antigen,
• wherein the administering reduces induction of pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-12, IFNα, IFNγ, IL-23, or any combination thereof.