Abstract: The present invention provides combination therapy using a binding agent that binds to human CD137 and to human PD-L1 in combination with a PD-1 inhibitor to reduce or prevent progression of a tumor or treating cancer.

Abstract: The present invention relates to antibodies capable of binding to human OX40 and to variants thereof comprising a modified Fc region comprising at least one mutation that enhances the Fc-Fc interaction of the antibody and at least one mutation that reduces the Fc effector functions of the antibody. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

Abstract: The present invention relates to antibodies capable of binding to human OX40 and to variants thereof comprising a modified Fc region comprising at least one mutation that enhances the Fc-Fc interaction of the antibody and at least one mutation that reduces the Fc effector functions of the antibody. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

Abstract: This disclosure relates to the field of therapeutic RNA to treat cancer, in particular advanced solid tumors such as metastatic (Stage IV) or unresectable localized cancer. Disclosed herein are compositions, uses, and methods for treatment of cancers. Administration of therapeutic RNAs to a patient having cancer disclosed herein can reduce tumor size, prolong time to progressive disease, and/or protect against metastasis and/or recurrence of the tumor and ultimately extend survival time.

Abstract: The present invention relates to combination therapy using a binding agent that binds to human CD40 and to human CD137 in combination with a checkpoint inhibitor to reduce or prevent progression of a tumor or treating cancer.

Abstract: The present disclosure relates to antibodies having the ability to bind to the immune checkpoint protein programmed death-1 (PD-1), such as human PD-1, or nucleic acids encoding such antibodies, wherein the antibodies comprise modifications in the Fc region eliminating or reducing a Fc-mediated effector function of the antibodies. The present disclosure also relates to compositions or kits comprising said antibodies or nucleic acids, as well as to the use of these antibodies or nucleic acids or compositions in the field of medicine, preferably in the field of immunotherapy, e.g., for the treatment of cancers. The present invention further relates to methods for inducing an immune response in a subject comprising providing to the subject an antibody of the present disclosure or one or more nucleic acids encoding such an antibody, or a composition comprising said antibody or nucleic acids.

Abstract: The present disclosure relates to antibodies having the ability of binding to the immune checkpoint protein programmed death-1 (PD-1), such as human PD-1, or nucleic acids encoding such antibodies. The present disclosure also relates to compositions or kits comprising said antibodies or nucleic acids, as well as to the use of these antibodies or nucleic acids or compositions in the field of medicine, preferably in the field of immunotherapy, e.g., for the treatment of cancers. The present invention further relates to methods for inducing an immune response in a subject comprising providing to the subject an antibody having the ability of binding to the immune checkpoint protein PD-1, such as human PD-1, or a nucleic acid encoding such an antibody, or a composition comprising said antibody or nucleic acid.

Abstract: The present disclosure relates to antibodies having the ability to bind to the immune checkpoint protein programmed death-1 (PD-1), such as human PD-1, or nucleic acids encoding such antibodies, wherein the antibodies comprise modifications in the Fc region eliminating or reducing a Fc-mediated effector function of the antibodies. The present disclosure also relates to compositions or kits comprising said antibodies or nucleic acids, as well as to the use of these antibodies or nucleic acids or compositions in the field of medicine, preferably in the field of immunotherapy, e.g., for the treatment of cancers. The present invention further relates to methods for inducing an immune response in a subject comprising providing to the subject an antibody of the present disclosure or one or more nucleic acids encoding such an antibody, or a composition comprising said antibody or nucleic acids.

Abstract: The present invention provides a binding agent that binds to EpCAM and to CD137 which is useful to treat or prevent a tumor or cancer, or to prevent progression of a tumor or cancer.

Abstract: The invention relates to variants of interleukin-2 (IL2). In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted such that affinity for the ?? IL2 receptor complex (IL2R??) is enhanced. In one embodiment, the human IL2 or functional variant thereof is further substituted such that affinity for the ??? IL2 receptor complex (IL2???) is reduced. In one embodiment, the polypeptide activates effector T cells over regulatory T cells.

Abstract: The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (?) subunit of the heterotrimeric IL2 receptor complex, IL2R???, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2R? variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2R???, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

Abstract: The present disclosure relates to methods and agents for enhancing the effect of immune effector cells, in particular immune effector cells that respond to interleukin-2 (IL2), for example effector T cells such as CD8+ T cells. Specifically, the present disclosure relates to methods comprising administering to a subject a polypeptide comprising IL2 or a functional variant thereof or a polynucleotide encoding a polypeptide comprising IL2 or a functional variant thereof and a polypeptide comprising type I interferon (IFN) or a functional variant thereof or a polynucleotide encoding a polypeptide comprising type I interferon or a functional variant thereof.

Abstract: The invention relates to variants of interleukin-2 (IL2). In one embodiment, the IL2 variants activate effector T cells over regulatory T cells. In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted at at least a position having an acidic or basic amino acid residue in wild type human IL2 that contacts the alpha subunit of the ??? IL2 receptor complex (I12K???). Alternatively, the mutein of human IL2 or of a functional variant of human IL2 comprises at least (i) one or more amino acid substitutions which reduce the affinity for the alpha subunit of II_2K??? and (ii) one or more amino acid substitutions which enhance the affinity for II_2K??.

Abstract: The present invention relates to cytokine fusion proteins and to nucleic acid molecules encoding such cytokine fusion proteins. The present invention further relates to cells, non-human organisms. pharmaceutical compositions and kits comprising the cytokine fusion proteins or the nucleic acid molecules encoding them, as well as to their use as medicaments.