NOVEL ANTI-TNFR2 AGONIST ANTIBODY MOLECULES

Abstract

Novel antibody molecules are described that specifically bind to TNFR2 on a target cell and thus agonize TNFR2, but do not block the binding of the TNF-α ligand to TNFR2; the use of such antibody molecules in medicine is also described, including in the treatment of cancer or chronic inflammatory diseases.

Description

NOVEL ANTI-TNFR2 AGONIST ANTIBODY MOLECULES FIELD OF INVENTION The present invention relates to novel agonist antibodies that specifically bind to the tumor necrosis factor receptor 2 (TNFR2), but do not block the binding of TNF-α ligand to TNFR2. The invention also relates to their use in medicine, such as in the treatment of cancer or chronic inflammatory diseases. BACKGROUND OF THE INVENTION Tumor necrosis factor (TNF) receptor 2 (TNFR2, TNFR-2, or TNFRII), also known as tumor necrosis factor receptor superfamily member IB (TNFRSF1B) and CD120b, is a membrane receptor that binds to tumor necrosis factor alpha (TNF-α or TNFα). It is found on the surface of T lymphocytes, monocytes, and macrophages, and can activate the proliferation of cells expressing the TNFR2 receptor via nuclear factor kappa B (NF-κB). Notably, TNFR2 is highly upregulated in cancer, particularly in tumor-infiltrating immune cells, such as regulatory T lymphocytes (Tregs), CD8+ cytotoxic effector T lymphocytes, and various myeloid cell subpopulations. TNFR2 has been analyzed as a promising target for cancer immunotherapy and has been described as being highly expressed on the surface of, among others, intratumoral Tregs and many human tumor cells (Williams GS et al., Oncotarget. 2016; 7(42): 68278-68291; Vanamee ES et al., Trends in Molecular Medicine, 2017, vol. 23, issue 11, 1037-1046; Frontiers in Immunology, November 2017 | Volume 8 | Article 1482, Sci Signal. January 2, 2018;11(511)). Regulatory T cells (also called Tregs, Tregs, or Tregs, and formerly known as suppressor T cells or suppressor regulatory T cells) are a subpopulation of T cells capable of suppressing other immune cells in both normal and pathological immune environments. Tregs are CD4-positive cells (CD4+ lymphocytes). There are other CD4+ T cells that are not Tregs; however, Tregs can be distinguished from non-Treg CD4+ cells because Tregs are also FOXP3-positive (FOXP3+), while non-Treg CD4+ cells are FOXP3-negative (FOXP3+). Tregs can also be separated from CD4+ non-Treg lymphocytes because Tregs are also CD25+CD127neg / low, whereas CD4+ non-Treg lymphocytes are CD25'CD127+ or CD25+CD127+. TNFR2 has also been analyzed in relation to autoimmune diseases LCLcnn / Lznz / E / Yi (Faustman DL et al., Front Immunol. 2013; 4: 478, Clin Trans Immunology. January 8, 2016;5(l):, J Neurosci. May 4, 2016;36(18):5128-43) and inflammatory diseases (Ait-Ali D et al., Endocrinology. June 2008;149(6):2840-52, Sci Rep. September 7, 2016;6:32834). Anti-TNFR2 antibodies of different types and with diverse characteristics have also been previously described. For example, Williams et al. (Oncotarget. October 18, 2016;7(42):68278-68291) describe ligand-blocking and non-ligand-blocking agonist antibodies. WO 2014 / 124134 discloses the use of a TNFR2 agonist, such as an anti-TNFR2 agonist antibody and / or an NF-κB activator, for the in vitro production of a CD4+CD25hi-enriched Treg composition. The composition is said to be useful in the treatment of immunological disorders or infectious diseases in patients. WO 2017 / 040312 discloses anti-TNFR2 antibodies and, in particular, anti-TNFR2 agonist antibodies, which are capable of promoting TNFR2 signaling and having an effect on Treg expansion or proliferation. WO 2017 / 040312 discloses antibodies that bind specifically to an epitope comprising the sequence KCSPG, but not to an epitope comprising the sequence KCRPG, thereby excluding the antibodies of US 9 821 010 discussed above, or alternatively, not to any other member of the TNFR superfamily. Agonist antibodies are said to be useful in the treatment of immunological diseases. WO 2017 / 040312 further establishes the complete sequence of human TNFR2. WO 2017 / 083525 discusses pharmacological compositions comprising anti-TNFR2 antibodies and their use in the treatment of disorders associated with TNF-α and / or TNFR2, such as cancer. WO 2017 / 083525 further discusses antibodies comprising a human IgG1 Fe domain that is null for binding to an Fcy receptor, and also for suppressing Treg expansion. In addition, anti-TNFR2 antibodies that are able to act as TNFR2 agonists are described in Galloway et al. (Eur. Immunol. 22:3045-3048, 1992), Tartaglia et al. (Biol. Chem.268:18542-18548, 1993), Tartaglia et al. (Immunol. 151:4637-4641, 1993), Smith et al. (Biol. Chem.269:9898-9905, 1994) and Amrani et al. (Am. Respir. Cell. Mol. Biol. 15:55-63, 1996). However, none of these documents teach or suggest TNFR2 agonist antibodies that bind specifically to TNFR2, but do not block the binding of the TNF-α ligand to the same TNFR2. Fe receptors are membrane proteins found on the cell surface of immune effector cells, including monocytes, macrophages, dendritic cells, neutrophils, mast cells, basophils, eosinophils, natural killer cells, and B lymphocytes. The name derives LCLcnn / Lznz / E / Yi of their specificity for binding to the Fe region of antibodies. Fe receptors are located on the cell membrane, also known as the plasma membrane or cytoplasmic membrane. Fe receptors can be subdivided into activating FcR and inhibitory FcR, which are known to coordinately regulate cell activation by binding Fe to aggregated immunoglobulin G and transmitting activating or inhibitory signals to the cell via intracellular ITAM or GTIM motifs. FcR binding to aggregated immunoglobulin or immune complexes can mediate antibody internalization into the cell and can result in antibody-mediated phagocytosis, antibody-dependent cell-mediated cytotoxicity, or antigen presentation or cross-presentation. FcRs are also known to mediate or enhance the cross-linking of cell surface receptors bound to antibodies.Such crosslinking is known to be necessary for some (Li et al. 2011. 'Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies', Science, 333: 1030-4.; White et al. 2011. 'Interaction with FcgammaRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody', J Immunoi, 187: 1754-63) but not all (Richman et al. 2014. 'Anti-human CD40 monoclonal antibody therapy is potent without FcR crosslinking', Oncoimmunology, 3: e28610) antibodies capable of activating signaling in target cells, and may or may not be necessary to achieve therapeutic effects. A subgroup of Fe receptors are the Fcy receptors (Fc-gamma receptors, FcgammaR, FcyR), which are specific for IgG antibodies. There are two types of Fcy receptors: activating Fcy receptors (also called activating Fcy receptors) and inhibitory Fcy receptors. Activating and inhibitory receptors transmit their signals through tyrosine-based immunoreceptor activation motifs (ITAMs) or tyrosine-based immunoreceptor inhibitory motifs (GTIMs), respectively. In humans, FcyRIIb (CD32b) is an inhibitory Fcy receptor, while FcyRI (CD64), FcyRIIa (CD32a), FcyRIIc (CD32c), and FcyRIIIa (CD16a) are activating Fcy receptors. FcygRIIIb is a GPI-linked receptor expressed on neutrophils that lacks an ITAM motif, but through its ability to cross-link with lipid rafts and interact with other receptors, it is also considered an activator. In mice, the activator receptors are FcyRI, FcyRIII, and FcyRIV. Antibodies are known to modulate immune cell activity through interaction with Fcγ receptors. Specifically, the way in which antibody immune complexes modulate immune cell activation is determined by their relative interaction with activating and inhibitory Fcγ receptors. Different antibody isotypes bind with different affinities to activating and inhibitory Fcγ receptors, resulting in different A:I ratios (activation-inhibition ratios) (Nimmerjahn et al., Science. December 2, 2005;310(5753): 1510-2). LCLcnn / Lznz / E / Yi By binding to inhibitory Fcy receptors, an antibody can inhibit, block and / or downregulate the functions of effector cells. By binding to an inhibitory FcγR, antibodies can further stimulate cell activation by aggregating antibody-directed signaling receptors on a target cell (L1 et al. 2011. 'Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies', Science, 333: 1030-4; White et al. 2011. 'Interaction with FcγγRIB is critical for the agonistic activity of anti-CD40 monoclonal antibody', J Immunol, 187: 1754-63; White et al. 2014. 'Fcγ receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overridden through antibody multimerization', J Immunol, 193: 1828-35). By binding to an activating Fcy receptor, an antibody can activate the functions of effector cells and thus trigger mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), cytokine release, and / or antibody-dependent endocytosis, as well as NETosis (i.e., activation and release of NETs, ​​neutrophil extracellular traps) in the case of neutrophils. The binding of an antibody to an activating Fcy receptor can also lead to an increase in certain activation markers, such as CD40, MHCII, CD38, CD80, and / or CD86. Recent data published by, among others, the inventors demonstrate a fundamental and differential dependence of the CD8 T cell agonist and anti-4β1BB antibodies that decrease Tregs for binding to activating and inhibiting FκC receptors, respectively, for therapeutic efficacy (Buchan et al., 'Antibodies to Costimulatory Receptor 4β1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function', Immunity 2018 49(5):958-970). Furthermore, and critically, the simultaneous administration of the CD8 T cell agonist and anti-4β1BB antibodies that decrease Tregs, optimized for binding to activating and inhibiting FκC receptors, respectively, altered therapeutic activity. These data demonstrate the critical importance of developing antibodies with appropriate and customized interactions of activating and inhibiting FκC receptors to maximize the therapeutic activity of antibodies with different mechanisms of action.At the same time, they demonstrate that suboptimal interaction of FcyR activators and inhibitors can severely reduce therapeutic efficacy. These data were surprising, as they contrasted with findings for antibodies against other TNFSR members, particularly immunostimulatory anti-CD40 antibodies, which show an obligatory need for interaction with inhibitory, but not activating, FcγR receptors (Lí et al. 2011. 'Inhibitory Fcγ receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies', Science, 333: 1030-4; White et al. 2011. 'Interaction with FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody', JImmunol, 187: 1754-63). Taken together, these results demonstrate that dependence The FcyR LCLcnn / Lznz / B / Yi can vary between antibodies against different targets of the same receptor superfamily, and even between different types of antibodies against the same target, in a way that is not easily predictable but may be critical to understand and take advantage of when developing antibodies for therapeutic use. BRIEF DESCRIPTION OF THE INVENTION In the work that led to the present invention, and also to a parallel invention, two large different groups of anti-TNFR2 antibodies with potent therapeutic effects and different characteristics and mechanisms of action were identified. The inventors first identified potent therapeutic activity in anti-TNFR2 antagonist antibodies that block the binding of TNF-α to the TNFR2 receptor. The activity of such antibodies was shown to depend on interactions with FcyR, and in particular on binding to activating FcyR, for therapeutic activity in vivo. This group or category of potent anti-TNFR2 therapeutic reagents was found to be characterized by 1) pronounced blockade and inhibition of TNF-α-induced TNFR2 signaling and 2) FcyR interaction-dependent activity, which is most strongly enhanced by the interaction of activating FcyRs with inhibitory FcyRs. The inventors then identified a distinct group of anti-TNFR2 antibodies with equally potent therapeutic activity in vivo, but whose characteristics are in many respects the opposite of those of the antagonistic and blocking TNFR2 antibodies that constitute the first group. The anti-TNFR antibodies in this second group do not depend on TNF-α blocking or inhibition of TNFR2 signaling for their therapeutic activity, but are instead characterized by strong activation of TNFR2 signaling. In further contrast to the blocking antibodies of the first group, the agonist antibodies of the second group do not exhibit an obligatory dependence on the antibody:FcεR interaction, although their activity is enhanced by antibody variants that interact with FcεR.In further contrast to the antagonist blocking antibodies of the first group, the agonist antibodies of the second group show the greatest activity in antibody variants with enhanced binding to inhibitor FcyR compared to activator. The present invention relates to the second group of anti-TNFR2 antibodies, namely, agonist antibody molecules that bind specifically to TNFR2 but do not block the binding of the TNF-α ligand to TNFR2. Such antibodies are potent therapeutic reagents and useful in medicine. The antagonist blocking antibodies that belong to the first group are used LCLcnn / Lznz / B / Yi in the Examples below for comparison with the non-blocking TNFR2 agonist antibody molecules of the present invention. In the Examples, other antibodies with some characteristics similar to those of the first or second group, or both, are also used for comparison purposes, as further explained below. Therefore, the present invention relates to agonist antibody molecules that specifically bind to TNFR2 on a target cell and do not block the binding of the TNF-α ligand to TNFR2. The present invention also relates to specific examples of such novel TNFR2 agonist antibody molecules. The present invention also relates to isolated nucleotide sequences encoding at least one of the above antibody molecules. The present invention also relates to plasmids comprising at least one of the above nucleotide sequences. The present invention also relates to viruses comprising at least one of the above nucleotide or plasmid sequences. The present invention also relates to cells comprising at least one of the above nucleotide sequences, at least one of the above plasmids, or at least one of the above viruses. The present invention also relates to the above antibody molecules, nucleotide sequences, plasmids, viruses and / or cells for use in medicine. The present invention also relates to the above antibody molecules, nucleotide sequences, plasmids, viruses and / or cells for use in medicine in the treatment of cancer or a chronic inflammatory disease. The present invention also relates to the use of the above antibody molecules, nucleotide sequences, plasmids, viruses and / or cells for use in medicine in the treatment of cancer or a chronic inflammatory disease. The present invention also relates to pharmaceutical compositions comprising or consisting of at least one of the above antibody molecules, nucleotide sequences, plasmids, viruses, and / or cells and, optionally, a pharmaceutically acceptable diluent, carrier, vehicle, and / or excipient. Such a pharmaceutical composition may be used in the treatment of cancer or a chronic inflammatory disease. The present invention also relates to methods for treating cancer or a chronic inflammatory disease in a subject comprising administering to the subject a therapeutically effective amount of at least one of the above antibody molecules, nucleotide sequences, plasmids, viruses and / or cells. LCLcnn / Lznz / B / Yi The present invention also relates to antibody molecules, antibody molecules for use, isolated nucleotide sequences, isolated nucleotide sequences for use, plasmids, plasmids for use, viruses, viruses for use, cells, cells for use, uses, pharmaceutical compositions and methods of treatment, as described herein with reference to the accompanying description, examples and / or figures. DETAILED DESCRIPTION OF THE INVENTION Therefore, the present invention relates to TNFR2 agonist antibody molecules that bind specifically to TNFR2, but do not block the binding of the TNF-α ligand to TNFR2. Preferably, the antibody molecules have intrinsic agonist activity. The agonist antibody molecules disclosed herein do not block the binding of TNF-α to TNFR2 and furthermore, they do not block TNFR2 signaling. It has been clearly demonstrated that TNF-α-mediated signaling through TNFR2 initiates a signaling cascade that culminates in the activation of the nuclear transcription factor NF-κB (Thommesen et al. Distinct differences between TNF receptor 1- and TNF receptor 2-mediated activation of NF-κB. J Biochem Mol Biol. May 31, 2005;38(3):281-9; Yang et al. Role of TNF-α Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications. Front Immunol. April 19, 2018;9:784). This, in turn, results in cell activation and the synthesis of several pro-inflammatory factors, one of which is IFN-γ in NK cells (Liu et al. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2. pii: 17023; Tato et al.Opposing roles of NFkappaB family members in the regulation of NK cell proliferation and production of IFN-gamma. Int Immunol. April 2006;18(4):505-13). Herein, the terms TNFR2 signaling and TNFR2 activation are used interchangeably. Antibody molecules bind specifically to TNFR2. An antibody is known to bind specifically to or interact with a defined target molecule or antigen, meaning that the antibody binds preferentially and selectively to its target and not to a non-target molecule. A TNFR2-specific antibody molecule refers to an antibody that binds to the TNFR2 protein in a dose-dependent manner, but not to an unrelated protein.Furthermore, the same antibody binds to cells that endogenously express TNFR2, and this binding can be blocked by pre-incubating the same cells with a commercially available polyclonal antibody reagent against TNFR2, demonstrating that non-specific binding cannot be detected when TNFR2 is masked by a polyclonal reagent. This is shown in Example 2. LCLcnn / Lznz / B / Yi The antibody molecule that specifically binds to TNFR2 (or the anti-TNFR2 antibody molecule) refers to an antibody molecule that specifically binds to at least one epitope in the extracellular domain of TNFR2. The terms antigen and cell surface epitope are expressions that someone with a mid-level background in immunology or cell biology will easily understand. A mid-level professional in biochemistry and immunology is familiar with methods for assessing protein binding. This professional will appreciate that these methods can be used to evaluate the binding of an antibody to a target and / or the binding of the Fe region of an antibody to an Fe receptor, as well as the relative potency, specificity, inhibition, prevention, or reduction of these interactions. Examples of methods that can be used to assess protein binding include immunoassays, BIAcore, Western blots, radioimmunoassay (RIA), enzyme-linked immunosorbent assays (ELISA), and flow cytometry (FACS). See Fundamental Immunology, second edition, Raven Press, New York, pages 332-336 (1989) for an analysis of antibody specificity. The target cells expressing TNFR2 to which the agonist antibody binds according to the present invention can be any immune cell expressing TNFR2, such as CD8-positive cells and myeloid cells. The effect of binding agonist antibody molecules according to the invention to TNFR2 may be the activation of T lymphocytes and / or myeloid cells; and / or the infiltration of T lymphocytes and / or myeloid cells into diseased tissue; and / or a change in the composition of T lymphocytes and / or myeloid cells in diseased tissue. The change in the composition of T lymphocytes and / or myeloid cells herein means different absolute or relative counts of various cell subpopulations, such as Tregs, CD8-positive cells, tumor-associated macrophages (TAMs) (including different subpopulations thereof), myeloid-derived suppressor cells (MDSCs), and / or pro-inflammatory macrophages. In this context, diseased tissue means tumor tissue (i.e., all cells in the tumor microenvironment, including tumor cells, immune cells, endothelial cells, and stromal cells) or tissue affected by a chronic inflammatory disease. To determine whether an antibody molecule blocks, or rather, in the context of the present invention, does not block, the binding of the ligand to TNFR2, an ELISA assay can be used to determine the amount of NF-α ligand bound to the immobilized TNFR2 receptor in the presence of specific antibodies against TNFR2. A non-blocking antibody will not prevent the binding of the ligand, TNF-α, to the immobilized TNFR2 receptor. This is demonstrated and explained in more detail in Example 3 below. More specifically, a non-blocking antibody molecule against TNFR2 according to the present invention is an antibody molecule that reduces the LCLcnn / Lznz / B / Yi TNF-α binding to TNFR2 is less than 50% compared to TNF-α binding in the presence of only one isotype control antibody molecule. In some embodiments, this is determined in a high-dose point ELISA or a dose-titration ELISA as shown in Example 3 and Figures 6A to 6E and 7A to 7E. Conversely, a blocking antagonist antibody molecule is a complete blocker, which is also capable of antagonizing TNFR2 signaling. Such antibody molecules are used for comparative purposes in the examples below. A complete blocker is defined herein as an antibody molecule that reduces TNF-α binding to TNFR2 by more than 98%, i.e., up to 100%, compared to TNF-α binding in the presence of only an isotype control antibody molecule. An isotype control antibody is an antibody produced against a protein or other structure that is not present in any form in the assay under study. The isotype control ideally has the same framework, but at least the same Fe portion, as the comparator antibodies. This is common knowledge for anyone with a mid-level understanding of the craft.In the examples described herein, the isotype control had the same framework, the same Fe portion, and was specific for fluorescein isothiocyanate (FUC). In some embodiments, the complete blocker reduces TNF-α binding by more than 99.5%. Other types of blockers are partial blockers and weak blockers. As used herein, a partial blocker is an antibody molecule that reduces TNF-α binding to TNFR2 by 60–98% compared to TNF-α binding in the presence of only an isotype control antibody molecule, and a weak blocker is an antibody molecule that reduces TNF-α binding to TNFR2 by less than 60%, such as 50–59.9%, compared to TNF-α binding in the presence of only an isotype control antibody molecule. In the examples, fully blocking antagonist antibody molecules, partially blocking antibody molecules, and weakly blocking antibody molecules are used for comparison with the non-blocking agonist antibody molecules of the present invention. Several properties and characteristics can underlie and (co)determine the biological activity of antibodies. In addition to the ability to block or not block ligand binding to the receptor, such important properties include the ability of antibody molecules to modulate receptor signaling—that is, to agonize or antagonize receptor signaling—and the dependence of antibodies on interactions with FcεR to confer therapeutic activity. First, the ability of complete blocking, partial blocking, and non-blocking antibodies to modulate TNFR2 signaling was characterized. Two extremes were identified. At the first extreme, antibodies were identified that completely blocked the LCLcnn / Lznz / E / Yi ligand-binding antibodies to TNFR2, which blocked TNF-α-induced TNFR2 signaling, and which by themselves did not induce signaling when bound to endogenously expressed TNFR2 in the cell. This group of antagonistic, ligand-blocking antibodies constitutes a separate invention and is included herein for comparative purposes. At the other extreme, antibodies were identified that do not block ligand binding to TNFR2, but, upon binding to TNFR2, caused endogenously expressing cells to agonize the receptor. This second group of antibodies forms the basis of the present invention. As used herein, a non-blocking antibody is an antibody molecule that reduces the binding of TNF-α to TNFR2 by 0-50% (such as 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50%, inclusive of all whole numbers and all intermediate decimal numbers) compared to the binding of TNF-α in the presence of only an isotype control antibody molecule. Antibodies and categories defined by partial blocking agonists, non-partial blocking agonists, and non-complete blocking antagonists were also identified, demonstrating the complex biology and great heterogeneity of anti-TNFR2 antibodies, clearly demonstrating that the antibodies of the present invention form a unique group. To determine whether an antibody has agonist or antagonist activity, a natural killer (NK) cell assay, as described in Example 4, can be used. Briefly, NK cells have been described as responding to IL-2 and IL-12 stimuli by secreting IFN-γ. Soluble TNF-α is produced endogenously and is present at robust but suboptimal concentrations (~100 pg / mL) for TNFR2 signaling, meaning that IFN-γ can increase and decrease by modulating TNFR2 signaling. Consequently, the exogenous addition of an optimal concentration of TNF-α that binds to TNFR2 enhances IFN-γ concentrations in this assay, as does incubation with an agonist anti-TNFR2 antibody. Conversely, co-incubation with anti-TNF-α antibody or ligand-blocking antagonist antibodies described herein for comparative purposes decreases IFN-γ release in this assay.Therefore, this assay can be used to identify the agonist or antagonist activity, or lack thereof, of anti-TNFR2 antibodies. (TNFR2 Augments Cytokine-Induced NK Cell IFNy Production through TNFR2. Almishri W. et al. J Innate Immun. 2016;8:617-629). Consequently, the ability of antibodies to agonize, i.e., induce TNFR2 signaling, can be monitored using this experimental setup. The ability of antibodies to induce signaling on their own after binding to TNFR2 in the same natural cell (NK) assay can be assessed by monitoring and comparing the increases in IFN-γ release with those observed after culturing in the presence or absence of exogenous TNF-α added at optimal signaling concentrations as described in Example 4. Therefore, an anti-TNFR2 agonist antibody can be defined as an antibody that enhances IFN-γ release by NK cells in this assay. An antibody with intrinsic agonist capacity enhances IFN-γ release by NK cells in a manner that is independent of antibody crosslinking or interactions with Feγ receptors, and is not dependent on the presence of soluble TNF-α ligand. Consequently, intrinsic agonist activity can be assessed using antibody formats that do not interact productively with FcyR, for example, aglycosylated antibodies carrying an N297A mutation in the Fe domain, or in assay / cell systems lacking FcyR. NK cells are well known to those in the mid-level profession (Binyamin, L., et al. (2008).Journal of Immunology 180, 6392-6401; Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy.). In this assay, an agonist antibody is defined as an antibody that results in a >100% (>2-fold) increase in IFN-γ release. Because this assay uses primary cells from PBMC donors, at least four donors must be included, and mean values ​​must be calculated for all donors. Cells from each donor to be included in the mean calculation must have responded to treatment with the positive control (soluble TNF-α) with IFN-γ levels increased >100% (>2-fold) relative to the isotype control treatment. The antibody agonist molecules described herein have intrinsic agonist activity, as explained above. In some embodiments of the present invention, it is preferred that the antibody enhance the release of IFN-γ by NK cells in the assay described above by at least 100%. In some embodiments, agonist activity can be enhanced by binding the antibody molecule to an Fcy receptor in addition to binding to TNFR2. In some such embodiments, non-blocking TNFR2 agonist antibody molecules bind with higher affinity to inhibitory Fcy receptors than to activating Fcy receptors. Higher affinity for inhibitory Fcy receptors than for activating Fcy receptors includes variants that bind with higher affinity to inhibitory Fcy receptors compared to individual activating Fcy receptors, for example, compared to any of FcyRIIA, FcyRIIIA, and FcyRI. The relatively high homology between mouse and human FcyR systems explains many of the general aspects of FcyR-mediated mechanisms conserved across species. However, mouse and human IgG subclasses differ in their affinities for their cognate FcyRs, which is important when translating FcyR-mediated observations in the mouse system to human IgG-based treatments for antibody-subclass targeting. LCLcnn / Lznz / B / Yi and / or a genetically engineered subclass variant, which exhibits adequate binding to FcyR activators compared to human inhibitors. The affinity and / or avidity of human antibody molecules to individual human FcyRs can be determined by surface plasmon resonance (SPR). In some embodiments, binding to an Fe receptor occurs through the normal interaction between the Fe region of the agonist antibody molecule and the Fe receptor. In some such embodiments, the antibody molecule is an IgG, which has an Fe region that binds to an Fcy receptor. In some of these embodiments, the anti-TNFRII antibody is of the human IgG2 isotype, which has an intermediate affinity similar to that of the human FcyRIIB inhibitor and the human FcyRIIA and FcyRIIIA activators, but does not interact productively with the human FcyRI activator. In some embodiments, the anti-TNFRII antibody is of the human IgG1 isotype, which binds to FcyRIIB with higher affinity compared to IgG2, but also binds to the human FcyRIIA activator with higher affinity, and furthermore binds to the FcyRI activator with high affinity.In other embodiments, the anti-TNFRII antibody is a human IgG genetically engineered to enhance binding to FcyRIIB, e.g., the SELF mutation (Chu et al. Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Mol Immunol. September 2008;45(15):3926-33) and / or genetically engineered for enhanced relative binding to FcyRIIB compared to FcyR activators, e.g., V9 or Vil mutations (Mimoto et al. Engineered antibody Fe variant with selectively enhanced FcyRIIb binding over both FcyRIIaR131 and FcyRIIaH131. Protein Eng Des Sel. October 2013; 26(10): 589-598).Genetically engineered IgG variants designed for enhanced binding to FcyRIIB inhibitor, or specifically enhanced binding affinity to FcyRIIB inhibitor but not to FcyRIIA activator, have been shown to increase in vivo agonist activity and therapeutic activity of the agonist antibody against CD40 CP-870,893 in animals humanized for FcyR activators and inhibitors (Dahan et al. 2016. 'Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcgammaR Engagement', Cancer Cell, 29: 820-31). The Fe receptor to which the agonist antibody molecule can bind in addition to TNFR2 is a receptor found on the surface of cells of myeloid origin, such as macrophages, monocytes, MDCS, neutrophils, mast cells, basophils or dendritic cells, or on the surface of lymphocytes, such as NK cells, B lymphocytes or certain T lymphocytes. As mentioned previously, antibody molecules often bind to Fe receptors via their FC regions. Since the agonist antibody molecules disclosed herein have intrinsic agonist activity, they do not need to bind to Fe receptors to agonize TNFR2. This means that in some embodiments of the present invention, LCLcnn / Lznz / E / Yi It is possible to use antibody molecules that do not depend on binding to the Fe receptor via their Fe region, and indeed, it is possible to use antibody molecules that do not have an Fe region. In some such embodiments, the antibody molecule may be a Fab'2 or a PEGYLATED version thereof. In some embodiments, the antibody molecules may be a divalent or multivalent antibody molecule comprising single-stranded antibodies, Fab, Fvs, scFv, Fab's, and / or (Fab')2. In other embodiments, the antibody molecules may comprise a modified Fe region, such as an aglycosylated variant of an IgG1 antibody molecule. Such aglycosylation may be achieved, for example, by an amino acid substitution of asparagine at position 297 (N297X) in the antibody chain.The substitution can be with a glutamine (N297Q), or with an alanine (N297A), or with a glycine (N297G), or with an asparagine (N297D), or with a serine (N297S). Other substitutions have been described, for example, by Jacobsen FW et al., JBC 2017, 292, 1865-1875, (see, for example, Table 1); such additional substitutions include L242C, V259C, A287C, R292C, V302C, L306C, V323C, I332C and / or K334C. In some embodiments, the antibody molecule against the TNFR2 agonist is an IgG1, IgG3, or IgG4 antibody molecule. In some embodiments, the anti-TNFR2 agonist antibody molecule is an IgG antibody molecule that exhibits enhanced binding to one or more Fe activating receptors and / or is genetically engineered for enhanced binding to one or more Fcy activating receptors and / or is genetically engineered for improved relative binding to Fcy activating receptors over inhibitors. In some embodiments, the anti-TNFR2 antibody is a genetically engineered human IgG1 antibody containing Fe.Examples of such genetically engineered antibody variants include afucosylated antibodies with enhanced selective antibody binding to FcyRIIIA and genetically engineered antibodies by targeted amino acid substitution, mutational or otherwise, resulting in enhanced binding to one or more activating Fcy receptors compared to the inhibitory FcyRIIB (Richards et al. 2008. Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells', Mol Cancer Ther, 7: 2517-27; Lazar et al. 2006. 'Engineered antibody Fe variants with enhanced effector function', Proc Nati Acad SciUSA, 103: 4005-10). In some embodiments, the human IgG antibody that is genetically engineered for enhanced binding to activating Fe gamma receptors may be a human IgG antibody carrying either the two S239D and I332E mutations, or the three S239D, I332E, and A330L mutations, and / or G236A mutations in its Fe portion. In some embodiments, the human IgG antibody that is genetically engineered for enhanced binding to the LCLcnn / Lznz / E / Yi Fe gamma activating receptors may be an afucosylated human IgG antibody. As explained previously, for antibody molecules to be intrinsic agonists means that they are agonists both in the absence and presence of TNF-α. In some embodiments, the antibody is an agonist in the absence of TNF-α. In some embodiments, the antibody is an agonist in the presence of TNF-α. The target cell expressing TNFR2 to which the agonist antibody is attached according to the present invention can be selected from the group consisting of immune cells or cancer cells expressing TNFR2. Those with a mid-level background in immunology and molecular biology are familiar with antibodies. Typically, an antibody comprises two heavy chains (H) and two light chains (L). This entire antibody molecule is sometimes referred to as a full-size or full-length antibody. The antibody heavy chain comprises one variable domain (VH) and three constant domains (CH1, CH2, and CH3), and the antibody light chain comprises one variable domain (VL) and one constant domain (CL). The variable domains (sometimes collectively called the Fv region) bind to the antibody's target, or antigen. Each variable domain comprises three loops, called complementarity-determining regions (CDRs), which are responsible for target binding. The constant domains are not directly involved in binding an antibody to an antigen but exhibit various effector functions.Based on the amino acid sequence of the constant region of their heavy chains, antibodies or immunoglobulins can be assigned to different classes. There are five main classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and in humans, several of these are further divided into subclasses (sotypes), for example, IgG1, IgG2, IgG3, and IgG4; IgA1 and IgA2. Another part of an antibody is the Fe region (also known as the crystallizable fragment domain), which comprises two of the constant domains from each of the antibody's heavy chains. As mentioned earlier, the Fe region is responsible for the interactions between the antibody and the Fe receptor. The term antibody molecule, as used herein, encompasses full-length or full-size antibodies, as well as functional fragments of full-length antibodies and derivatives of such antibody molecules. Functional fragments of a full-size antibody have the same antigen-binding characteristics as the corresponding full-size antibody and include the same variable domains (i.e., the VH and VL sequences) and / or the same CDR sequences as the corresponding full-size antibody. A functional fragment does not always contain all six CDRs of a corresponding full-size antibody. LCLcnn / Lznz / B / Yi molecules containing three or fewer CDR regions (in some cases, even a single CDR or a part thereof) are capable of retaining the antigen-binding activity of the antibody from which the CDRs are derived. For example, in Gao et al., 1994, J. Biol. Chem., 269: 32389-93, it is described that a complete VL chain (including all three CDRs) has a high affinity for its substrate. For example, in Vaughan and Sollazzo 2001, Combinatoria! Chemistry & High Throughput Screening, 4: 417-430, molecules containing two CDR regions are described. On page 418 (right column, 3 Our Strategy for Design), a minibody is described that includes only the hypervariable CDR regions H1 and H2 sandwiched within the framework regions. The minibody is described as capable of targeting. Vaughan & Sollazzo refer to Pessi et al., 1993, Nature, 362: 367-9 and Bianchi et al., 1994, J. Mol. Biol., 236: 649-59, which describe the H1 and H2 minibody and its properties in more detail. Qiu et al., 2007, Nature Biotechnology, 25:921-9, demonstrates that a molecule consisting of two linked CDRs is capable of binding to the antigen. Quiocho, 1993, Nature, 362: 293-4, provides an overview of minibody technology.Ladner 2007, Nature Biotechnology, 25:875-7 comments that molecules containing two CDRs are able to retain antigen-binding activity. Antibody molecules containing a single CDR region are described, for example, in Laune et al., 1997, JBC, 272: 30937-44, where a range of hexapeptides derived from a single CDR are shown to exhibit antigen-binding activity, and it is noted that synthetic peptides from a single, complete CDR exhibit strong binding activity. Monnet et al., 1999, JBC, 274: 3789-96, show that a range of peptides from 12-mer and associated frame regions have antigen-binding activity, and it is noted that a single CDR3-like peptide is capable of binding to the antigen. In Heap et al., 2005, J. Gen. ViroL, 86: 1791-1800, it is reported that a microantibody (a molecule containing a single CDR) is capable of binding to the antigen, and it is shown that a cyclic peptide of an anti-HIV antibody has antigen-binding activity and function.In Nicaise et al., 2004, Protein Science, 13:1882-91, it is shown that a single CDR can confer antigen-binding activity and affinity to its lysozyme antigen. Therefore, antibody molecules that have five, four, three or fewer CDRs are able to retain the antigen-binding properties of the full-length antibodies from which they are derived. The antibody molecule can also be a derivative of a full-length antibody or a fragment of such an antibody. When a derivative is used, it must have the same antigen-binding characteristics as the corresponding full-length antibody, meaning it binds to the same epitope on the target as the full-length antibody. Therefore, by using the term antibody molecule, as used in the LCLcnn / Lznz / E / Yi present, includes all types of antibody molecules and functional fragments thereof and derivatives thereof, including: monoclonal antibodies, polyclonal antibodies, synthetic antibodies, recombinantly produced antibodies, multispecific antibodies, bispecific antibodies, human antibodies, antibodies of human origin, humanized antibodies, chimeric antibodies, single-chain Fv (scFv), Fab fragments, F(ab')2 fragments, F(ab') fragments, disulfide-linked Fv (sdFv), antibody heavy chains, antibody light chains, antibody heavy chain homodimers, antibody light chain homodimers, antibody heavy chain heterodimers, antibody light chain heterodimers, and antigen-binding functional fragments of such homo- and heterodimers. Furthermore, the term antibody molecule, as used herein, includes all classes of antibody molecules and functional fragments, including: IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgD, and IgE, unless otherwise specified. In some embodiments, the antibody molecule is a human antibody molecule, a humanized antibody molecule, or an antibody molecule of human origin. In some such embodiments, the antibody molecule is an IgG antibody. Optimal costimulation of TNFR superfamily agonist receptors, such as TNFR2, is known to depend on antibody interaction with the inhibitory FcyRII receptor. In mice, the IgG1 isotype, which binds preferentially to the inhibitory Fe gamma receptor (FcyRIIB) and only weakly to activating Fe gamma receptors, is known to be optimal for the costimulatory activity of monoclonal antibodies targeting the TNFR superfamily. Although a direct human equivalent of the mouse IgG1 isotype has not been described, antibodies can be genetically engineered to exhibit similarly enhanced binding to inhibitory human Fe gamma receptors over activating receptors.Such genetically engineered antibodies targeting the TNFR superfamily also exhibit enhanced in vivo costimulatory activity in transgenic mice genetically engineered to express activating and inhibitory human Fe gamma receptors (Dahan et al., 2016, Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcεR Engagement. Cancer Ceii 29(6):820-31). In some embodiments, the antibody molecule is therefore of an isotype that interacts optimally with inhibitory Fe receptors. In some embodiments, the antibody molecule is an IgG2 antibody. In some embodiments, the agonist antibody molecule that specifically binds to TNFR2 can be a llama antibody, and in particular a llama hdgG. Like all mammals, camelids produce conventional antibodies composed of two heavy chains and two light chains linked together by Y-shaped disulfide bonds. LCLcnn / Lznz / E / Yi (IgGi). However, they also produce two unique subclasses of immunoglobulin G, IgG2 and IgGs, also known as heavy chain IgG (hdgG). These antibodies are composed of only two heavy chains that lack the CH1 region but still have an antigen-binding domain at their N-terminus called VhH. Conventional Ig requires the association of variable regions of heavy and light chains to allow for a wide variety of antigen-antibody interactions. While isolated heavy and light chains still exhibit this capacity, they have very low affinity compared to paired heavy and light chains. The unique feature of hdgG is the ability of its monomeric antigen-binding regions to bind to antigens with specificity, affinity, and especially diversity that are comparable to conventional antibodies without the need to pair with another region. As described above, the invention encompasses different types and forms of antibody molecules, which will be familiar to those with a mid-level understanding of immunology. It is known that antibodies used for therapeutic purposes are often modified with additional components that alter the properties of the antibody molecule. Accordingly, it is included that an antibody molecule described herein or an antibody molecule used as described herein (e.g., a monoclonal antibody molecule, and / or a polyclonal antibody molecule, and / or a bispecific antibody molecule) comprises a detectable portion and / or a cytotoxic portion. A detectable portion includes one or more of the following: an enzyme; a radioactive atom; a fluorescent portion; a chemiluminescent portion; or a bioluminescent portion. The detectable portion allows the antibody molecule to be visualized in vitro, in vivo, and / or ex vivo. The cytotoxic portion includes a radioactive portion, and / or an enzyme, for example, where the enzyme is a caspase, and / or a toxin, for example, where the toxin is a bacterial toxin or poison; where the cytotoxic portion can induce cell lysis. It is also included that the antibody molecule may be in isolated and / or purified form, and / or may be PEGylated. PEGylation is a method by which polyethylene glycol polymers are added to a molecule such as an antibody molecule or derivative to modify its behavior, for example, to extend its half-life by increasing its hydrodynamic size, thus preventing renal clearance. As discussed previously, the CDRs of an antibody bind to the antibody target. The amino acid assignment to each CDR described herein is in accordance with the definitions according to Kabat EA et al. 1991, in Sequences of Proteins of Immunological Interest, fifth edition, NIH Publication No. 91-3242, pages xv-xviii. As someone in a mid-level trade will know, there are also other methods for LCLcnn / Lznz / B / Yi assign amino acids to each CDR. For example, the international information system ImMunoGeneTics (IMGT(R)) (http: / / www.imgt.org / and Lefranc and Lefranc The Immunoglobulin FactsBook published by Academic Press, 2001). In some embodiments, the antibody molecule that specifically binds to TNFR2 is a human antibody. In some embodiments, the antibody molecule that specifically binds to TNFR2 is a human-derived antibody, i.e., an originally human antibody that has been modified as described herein. In some embodiments, the antibody molecule that specifically binds to TNFR2 is a humanized antibody, that is, an originally non-human antibody that has been modified to increase its similarity to a human antibody. Humanized antibodies can be, for example, murine antibodies or llama antibodies. In some embodiments, the antibody molecule that specifically binds to TNFR2 is a human IgG2 antibody molecule. In some embodiments, the anti-TNFR2 antibody is an antibody in the form of a human IgG2 antibody that exhibits enhanced binding to one or more activating Fe receptors and / or is genetically engineered for enhanced binding to one or more activating Fe receptors; accordingly, in some embodiments, the anti-TNFR2 antibody is a genetically engineered human IgG2 antibody with Fe. In some embodiments, the anti-TNFR2 antibody is a murine or humanized murine IgG3 antibody. In some embodiments, the anti-TNFR2 antibody is a monoclonal antibody. In some embodiments, the anti-TNFR2 antibody is a polyclonal antibody. In some embodiments, the antibody molecule that specifically binds to TNFR2 is a human IgG1 antibody molecule, which corresponds to a murine IgG2a. In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VH-CDR1 sequences listed in Table 1 below. In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VH-CDR2 sequences listed in Table 1 below. LCLcnn / Lznz / E / Yi In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VH-CDR3 sequences listed in Table 1 below. In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VL-CDR1 sequences listed in Table 1 below. In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VL-CDR2 sequences listed in Table 1 below. In some embodiments, the antibody molecule that specifically binds to TNFR2 comprises one of the VL-CDR3 sequences listed in Table 1 below. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule selected from the group consisting of antibody molecules comprising 6 CDRs selected from the group consisting of: SEQ ID NO: 1, 2, 3, 4, 5 and 6; SEQ ID NO: 9, 10, 11, 12, 13 and 14; SEQ ID NO: 17, 18, 19, 20, 21 and 22; SEQ ID NO: 25, 26, 27, 28, 29 and 30; SEQ ID NO: 33, 34, 35, 36, 37 and 38; SEQ ID NO: 41, 42, 43, 44, 45and 46; SEQ ID NO: 49, 50, 51, 52, 53 and 54; SEQ ID NO: 57, 58, 59, 60, 61 and 62; SEQ ID NO: 65, 66, 67, 68, 69 and 70; SEQ ID NO: 73, 74, 75, 76, 77 and 78; SEQ ID NO: 81, 82, 83, 84, 85 and 86; SEQ ID NO: 89, 90, 91, 92, 93 and 94; and SEQ ID NO: 97, 98, 99, 100,101 and 102. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule comprising 6 CDRs having SEQ ID NO: 1, 2, 3, 4, 5 and 6; or an antibody molecule comprising the 6 CDRs having SEQ ID NO: 9, 10, 11, 12, 13 and 14; or an antibody molecule comprising the 6 CDRs having SEQ ID NO: 17, 18, 19, 20, 21 and 22; or an antibody molecule comprising the 6 CDRs having SEQ ID NO: 25, 26, 27, 28, 29 and 30; or an antibody molecule comprising the 6 CDRs having SEQ ID NO: 33, 34, 35, 36, 37 and 38; or an antibody molecule comprising the 6 CDRs having SEQ ID NO: 41, 42, 43, 44, 45 and 46. LCLcnn / Lznz / E / Yi In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule comprising 6 CDRs having SEQ ID NO: 1, 2, 3, 4, 5 and 6. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule selected from the group consisting of antibody molecules comprising a VH selected from the group consisting of SEQ ID NO: 7, 15, 23, 31, 39, 47, 55, 63, 71, 79, 87, 95 and 103. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule selected from the group consisting of antibody molecules comprising a VL selected from the group consisting of SEQ ID NO: 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule comprising a VH having SEQ ID NO: 7, 15, 23, 31, 39 or 47. In some embodiments, the anti-TNFR2 antibody molecule is an antibody molecule comprising a VH having SEQ ID NO: 7. In some embodiments, it is preferred that the antiTNFR2 antibody molecule be an antibody molecule comprising a VL having SEQ ID NO: 8, 16, 24, 32, 40 or 48. In some embodiments, it is of higher preference that the anti-TNFR2 antibody molecule be an antibody molecule comprising a VL having SEQ ID NO: 8. In some embodiments, it is preferred that the antiTNFR2 antibody molecule comprise a VH having SEQ ID NO: 7 and a VH having SEQ ID NO: 8. In some embodiments, the anti-TNFR2 antibody molecule comprises a CH having SEQ ID NO: 217. In some embodiments, the anti-TNFR2 antibody molecule comprises a CL having SEQ ID NO: 218. In some embodiments, the anti-TNFR2 antibody molecule comprises a VH having SEQ ID NO: 7, a VH having SEQ ID NO: 8, a CH having SEQ ID NO: 217, and a CL having SEQ ID NO: 218. LCLcnn / Lznz / E / Yi Table 1: specific sequences of antibody molecules against TNFR2 agonists that do not block the binding of TNF-q to TNFR2 as described herein (in sequences VH v VL, the CDR sequences are marked in bold) LCLcnn / Lznz / B / Yi Clon de anticuerpo Región Secuencia SEQ ID NO: 001-F02 VH-CDR1 FSDYYMSWVRQAPG 1 VH-CDR2 ANINTDGSEKYYLDSVKGR 2 VH-CDR3 AREEYGAFDI 3 VL-CDR1 CSGSSSNIGSNTVN 4 VL-CDR2 DNNKRPS 5 VL-CDR3 CQSFDRGLSGSIV 6 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPG KGLEWVANINTDGSEKYYLDSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAREEYGAFDIWGQGTLVTVSS 7 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGT APKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CQSFDRGLSGSIVFGGGTKLTVLG 8 001-F06 VH-CDR1 FSSYAMHWVRQAPG 9 VH-CDR2 SAISGGATTTYYADSVKGR 10 VH-CDR3 AKGGTGDPYYFDY 11 VL-CDR1 CTGSSSNIGAGYDVH 12 VL-CDR2 RNNQRPS 13 VL-CDR3 CAARDDGLSGPV 14 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPG KGLEWVSAISGGATTTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCAKGGTG DPYYFDYWGQGTLVTVSS 15 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCAARDDG LSG PVFGGGTKLTVLG 16 001-B05 VH-CDR1 FSNAWMSWVRQAPG 17 VH-CDR2 SSISSASGYIYYGDSVKGR 18 VH-CDR3 ARGTLYGDFDEF 19 VL-CDR1 CSGSSSNIGNNAVN 20 VL-CDR2 GNTNRPS 21 VL-CDR3CQSYDSSLSGYVV 22 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPG KGLEWVSSISSASGYIYYG DSVKG RFTISRDNSKNTLYLQM N N LRAEDTAVYYCARGTLYG DFDEFWGQGTLVTVSS 23 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNAVNWYQQLPG TAPKLLIYGNTNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADY YCQSYDSSLSGYWFGGGTKLTVLG 24 001-C05 VH-CDR1 FSSNEMSWIRQAPG 25 VH-CDR2 SVIYSGGSTYYADSVKGR 26 VH-CDR3 ARREGWLVPFDY 27 VL-CDR1 CSGSSSNIGSNTVN 28 VL-CDR2 GNIIRPS 29 VL-CDR3 CQSFDTTLSGSIV 30 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSNEMSWIRQAPGK GLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLR AEDTAVYYCARREGWLVPFDYWGQGTLVTVSS 31 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGT APKLLIYGNIIRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYC QSFDTTLSGSIVFGGGTKLTVLG 32 004-E08 VH-CDRÍ FSRYWMHWVRQVPG 33 VH-CDR2 SGISDSGVVTYYADSVKGR 34 VH-CDR3 ARAQSVAFDI 35 VL-CDR1 CSGSSSNIGAGHDVH 36 VL-CDR2 YDDLLPS 37 VL-CDR3 CAAWDDSLSGWV 38 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYWMHWVRQVPG KGLEWVSGISDSGWTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARAQSVAFDIWGQGTLVTVSS 39 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGAGHDVHWYQQLP GTAPKLLIYYDDLLPSGVPDRFSGSKSGTSASLAISGLRSEDEADY YCAAWDDSLSGWVFGGGTKLTVLG 40 001-G05 VH-CDRI FSSYAMSWVRQAPG 41 VH-CDR2 SVISGSGGSTYYADAVKGR 42 VH-CDR3 TTDSGSGSYL 43 VL-CDR1 CTGSSSNIGAGYDVH 44 VL-CDR2 SNNQRPS 45 VL-CDR3 CAAWDDSLNGPV 46 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGK GLEWVSVISGSGGSTYYADAVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCTTDSGSGSYLWGQGTLVTVSS 47 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCAAWDDSLNG PVFGGGTKLTVLG 48 001-A09 VH-CDRÍ FSSNYMSWVRQAPG 49 VH-CDR2 SVISGSGGSTYYADSVKGR 50 VH-CDR3 ARDRGWFDP 51 VL-CDR1 CSGSRSNIDNSYVS 52 VL-CDR2 RNNQRPS 53 VL-CDR3 CATWDDSLSGPV 54 VHEVQLLESGGGLVQPGGSLRLSCAASGFTFSSNYMSWVRQAPG KGLEWVSVISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARDRGWFDPWGQGTLVTVSS 55 VL QSVLTQPPSASGTPGQRVTISCSGSRSNIDNSYVSWYQQLPGT APKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CATWDDSLSG PVFGGGTKLTVLG 56 001-B09 VH-CDRI FSRHAMNWVRQAPG 57 VH-CDR2 SSISTGSSYIDYADSVKGR 58 VH-CDR3 AREKGHYYYGMDV 59 VL-CDR1 CTGSSSNIGAGYDVH 60 VL-CDR2 GNSYRPS 61 VL-CDR3 CQSYDTSLSAYVV 62 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSRHAMNWVRQAPG KGLEWVSSISTGSSYIDYADSVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCAREKG HYYYG M DVWGQGTLVTVSS 63 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYGNSYRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCQSYDTSLSAYVVFGGGTKLTVLG 64 lc Lcnn / Lznz / E / γΐΛΐ 001-C03 VH-CDR1 FSNAWMSWVRQAPG 64 VH-CDR2 SAISVSGINTYYADSVKGR 66 VH-CDR3 ARDTGSLGVDY 67 VL-CDR1 CSGSSSNIGSNTVN 68 VL-CDR2 RNNQRPS 69 VL-CDR3 CQSYDSSLSISV 70 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVR QAPGKGLEWVSAISVSGINTYYADSVKGRFTISRDNSKNT LYLQMNSLRAEDTAVYYCARDTGSLGVDYWGQGTLVTVS S 71 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQL PGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRS EDEADYYCQSYDSSLSISVFGGGTKLTVLG 72 001-A10 VH-CDR1 FSDYYMTWIRQAPG 73 VH-CDR2 SSISGGSTYYADSRKGR 74 VH-CDR3 AREPGYSYGFFDY 75 VL-CDR1 CTGSSSNIGAGYDVH 76 VL-CDR2 SNNQRPS 77 VL-CDR3 CQSYDRSLSGSIV 78 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMTWIRQ APGKGLEWVSSISGGSTYYADSRKGRFTISRDNSKNTLYL QMNSLRAEDTAVYYCAREPGYSYGFFDYWGQGTLVTVSS 79 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQ QLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGL RSEDEADYYCQSYDRSLSGSIVFGGGTKLTVLG 80 001-006 VH-CDR1 SSSYWMSWVRQAPG 81 VH-CDR2 SAISGSGGSTYYADSVKGR 82 VH-CDR3 AREYSGYEFDF 83 VL-CDR1 CTGSSSNIGARSDVH 84 VL-CDR2 GNRNRPS 85 VL-CDR3 CQSFDRGLSGSIV 86 VHEVQLLESGGGLVQPGGSLRLSCAASGFTSSSYWMSWVR QAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKN TLYLQMNSLRAEDTAVYYCAREYSGYEFDFWGQGTLVTV SS 87 VL QSVLTQPPSASGTPGQRVTISCTGSSNIGARSDVHWYQ QLPGTAPKLLIYGNRNRPSGVPDRFSGSKSGTSASLAISGL RSEDEADYYCQSFDRGLSGSIVFGGGTKLTVLG 88 001-H03 VH-CDR1 FSSNYMSWVRQAPG 89 VH-CDR2 SSISSSSSYIYYADSVKGR 90 VH-CDR3 ARDRGRTGTDY 91 VL-CDR1 CSGTTSNIGSYAVN 92 VL-CDR2 GNINRPS 93 VL-CDR3 CQSYDSSLSASL 94 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSNYMSWVRQ APGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCARDRGRTGTDYWGQGTLVTVSS 95 VL QSVLTQPPSASGTPGQRVTISCSGTTSNIGSYAVNWYQQL PGTAPKLLIYGNINRPSGVPDRFSGSKSGTSASLAISGLRS EDEADYYCQSYDSSLSASLFGGGTKLTVLG 96 lc Lcnn / Lznz / E / γΐΛΐ 005-A05 VH-CDR1 FSSYAMSWVRQAPG 97 VH-CDR2 STIIGSGANTWYADSVKGR 98 VH-CDR3 ARHEGYYYYGMDV 99 VL-CDR1 CTGSSSNIGAGYVVH 100 VL-CDR2 GNSNRPS 101 VL-CDR3 CAAWDDSLNGRV 102 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQ APGKGLEWVSTIIGSGANTWYADSVKGRFTISRDNSKNTL YLQMNSLRAEDTAVYYCARHEGYYYYGMDVWGQGTLVT VSS 103 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYVVHWYQ QLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGL RSEDEADYYCAAWDDSLNGRVFGGGTKLTVLG 104 LCLcnn / Lznz / B / Yi To determine or demonstrate the characteristics of the antibody molecules of the present invention, they were compared with antibody molecules that block the binding of TNF-α to TNFR2. Such antibodies are shown in Table 2. Table 2: Specific sequences of antibody molecules against TNFR2 blockers referred to herein as reference antibodies (in sequences VH and VL, the CDR sequences are marked in bold) Antibody Clone Region Sequence SEQ ID NO: 001-H10 VH-CDR1 FDDYGMSWVRQAPG 105 VH-CDR2 SVIYSGGSTYYADSVKGR 106 VH-CDR3 CARDRSSSWYRDGMDV 107 VL-CDR1 CTGSSSNIGAGYDVH 108 VL-CDR2 GNSNRPS 109 VL-CDR3 CAAWDDSLSGWV 110 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYGMSWVRQAPG KGLEWVSVIYSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCARDRSSSWYRDG M DVWGQGTLVTVSS 111 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCAAWDDSLSGWVFGGGTKLTVLG 112 004-H02 VH-CDR1 FDDYGMSWVRQAPG 113 VH-CDR2 STIYSGDNAYYGASVRGR 114 VH-CDR3 ARVYSSSWRKRAFDI 115 VL-CDR1 CSGTSSNIESNTVN 116 VL-CDR2 SDNQRPS 117 VL-CDR3 CAAWDDSLSGWV 118 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFDDYGMSWVRQAPG KGLEWVSTIYSGDNAYYGASVRGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCARVYSSSWRKRAFDIWGQGTLVTVSS 119 VL QSVLTQPPSASGTPGQRVTISCSGTSSNIESNTVNWYQQLPGT APKLLIYSDNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CAAWDDSLSGWVFGGGTKLTVLG 120 005-B02 VH-CDR1 FSDYYMSWIRQAPG 121 VH-CDR2 ALIWYDGGNEYYADSVKGR 122 VH-CDR3 VRETGNYGMDV 123 VL-CDR1 CTGSSSNIGAGYDVH 124 VL-CDR2 RNNQRPS 125 VL-CDR3 CATWDDRVNGPV 126 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWIRQAPGK GLEWVALIWYDGG N EYYADSVKG RFTISRDNSKNTLYLQM N SLRAEDTAVYYCVRETGNYGMDVWGQGTLVTVSS 127 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCATWDDRVNG PVFGGGTKLTVLG 128 005-B08 VH-CDR1 FSDYYMSWIRQAPG 129 VH-CDR2 AIISYDGGGKYFADPVKGR 130 VH-CDR3 ARYYGDGGFDP 131 VL-CDR1 CTGSSSNIGAGYVVH 132 VL-CDR2 SNNQRPS 133 VL-CDR3 CAAWDDSLNGPV 134 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWIRQAPGK GLEWVAIISYDGGGKYFADPVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCARYYGDGGFDPWGQGTLVTVSS 135 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYWHWYQQLPG TAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADY YCAAWDDSLNG PVFGGGTKLTVLG 136 001-E06 VH-CDR1 FSSNYMSWVRQAPG 137 VH-CDR2 ALIWYDGSNKYYADSVKGR 138 VH-CDR3 AKDPLFDS 139 VL-CDR1 CTGRSSNIGAGYDVH 140 VL-CDR2 DNNKRPS 141 VL-CDR3 CAAWDDSLNGPV 142 VHEVQLLESGGGLVQPGGSLRLSCAASGFTFSSNYMSWVRQAPG KGLEWVALIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCAKDPLFDSWGQGTLVTVSS 143 VL QSVLTQPPSASGTPGQRVTISCTGRSSNIGAGYDVHWYQQLP GTAPKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCAAWDDSLNG PVFGGGTKLTVLG 144 001-G04 VH-CDR1 FNTYSMNWVRQAPG 145 VH-CDR2 SVLYSDDDTHYADSVKGR 146 VH-CDR3 ARDCGGDCHSGDDAFDI 147 VL-CDR1 CSGSSSNIGSNTVN 148 VL-CDR2 DNDKRPS 149 VL-CDR3 CAAWHDSLNGWV 150 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFNTYSMNWVRQAPG KGLEWVSVLYSDDDTHYADSVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCARDCGG DCHSG DDAFDIWGQGTLVTVSS 151 VL QSVLTQPPSASGTPGQRVTICSGSSSSNIGSNTVNWYQQLPGT APKLLIYDNDKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CAAWH DSLNG WVLGGGTKLTVLG 152 lc Lcnn / Lznz / E / γΐΛΐ 001-G10 VH-CDR1 FSAYGMHWVRQAPG 153 VH-CDR2 AVVSYDGREKHYADSVKGR 154 VH-CDR3 ARSDGGYDSDSGYY 155 VL-CDR1 CSGSTSNIGSNFVY 156 VL-CDR2 DNNKRPS 157 VL-CDR3 CSSYAYSDNIL 158 VH EVQLLESGGGLVQPGG5LRLSCAASGFTFSAYGMHWVRQAPG KGLEWVAVVSYDGREKHYADSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCARSDGGYDSDSGYYWGQGTLVTVSS 159 VL QSVLTQPPSASGTPGQRVTISCSGSTSNIGSNFVYWYQQLPGT APKLLIYDNNKRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CSSYAYSDNILFGGGTKLTVLG 160 001-C08 VH-CDR1 FSNAWMSWVRQAPG 161 VH-CDR2 SGISSSGSSAYYADSVKGR 162 VH-CDR3 ARHYYYHIAGYYYDTFDI 163 VL-CDR1 CSGSSSNIGGNTVN 164 VL-CDR2 GNTNRPS 165 VL-CDR3 CAAWDDSLSGW 166 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPG KGLEWVSGISSSGSSAYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARHYYYHIAGYYYDTFDIWGQGTLVTVSS 167 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGGNTVNWYQQLPGT APKLLIYGNTNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CAAWDDSLSGWFGGGTKLTVLG 168 001-H09 VH-CDR1 FSSYAMSWVRQAPG 169 VH-CDR2 ATISYHGSDKDYADSVKGR 170 VH-CDR3 ARDANYHSSGYYYDVFDI 171 VL-CDR1 CSGSSSNIGSNTVN 172 VL-CDR2 GNSNRPS 173 VL-CDR3CAAWDDSLSTWV 174 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGK GLEWVATISYHGSDKDYADSVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCARDANYHSSGYYYDVFDIWGQGTLVTVSS 175 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGT APKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CAAWDDSLSTWVFGGGTKLTVLG 176 005-F10 VH-CDR1 FSDYYMTWIRQAPG 177 VH-CDR2 SGISGSGGYIHYADSVKGR 178 VH-CDR3 AREGLLPDAFD 179 VL-CDR1 CSGSSSNIGNNYVS 180 VL-CDR2 RNNQRPS 181 VL-CDR3 CAAWDDSVSGWV 182 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMTWIRQAPGK GLEWVSGISGSGGYIHYADSVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCAREGLLPDAFDIWGQGTLVTVSS 183 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGT APKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CAAWDDSVSGWVFGGGTKLTVLG 184 001-Β11 VH-CDR1 FSSYSMNWVRQAPG 185 VH-CDR2 AVMSYDEYNTYYADSVKG R 186 VH-CDR3 AKGFYGDYPLWDY 187 VL-CDR1 CSGGNSNIGTNTVD 188 VL-CDR2 SNNQRPS 189 VL-CDR3 CAAWDDSVNGPV 190 VH EVQLLESSGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPG KGLEWVAVMSYDEYNTYYADSVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYCAKG FYG DYPLWDYWGQGTLVTVSS 191 VL QSVLTQPPSASGTPGQRVTISCSGGNSNIGTNTVDWYQQLPG TAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAIGSLRSEDEADY YCAAWDDSVNG PVFGGGTKLTVLG 192 001-C07 VH-CDR1 FSSYEMNWVRQAPG 193 VH-CDR2 STITGGGSIYDANSVQGR 194 VH-CDR3 ARDSTYHSSGYYYDVFDI 195 VL-CDR1 CSGSSSNIGSNTVN 196 VL-CDR2 GNSNRPS 197 VL-CDR3 CAAWDDSLSGHWV 198 VH EVQLLESSGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPG KGLEWVSTITGGGSIYDANSVQGRFTISRDNSKNTLYLQMNSL RAEDTAVYCARDSTYHSSGYYYDVFDIWGQGTLVTVSS 199 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGT APKLLIYGNSNRPSPDRGVFSGSKSGTSASLAISGLRSDEADYY CAAWDDSLSG H WVFGGGTKLTVLG 200 001-D01 VH-CDR1 FSSYGMHWVRQAPG 201 VH-CDR2 SAVFGSGHGNTFYADAVKGR 202 VH-CDR3 AREQLWFGQDAFDI 203 VL-CDR1 CSGSSSNIGSNTVN 204 VL-CDR2 GNSNRPS 205 VL-CDR3CQSYDSSLSASV 206 VH EVQLLESGGGLVQPGGPLRLSCAASGFTFSSYGMHWVRQAPG KGLEWVSAVFGSGHGNTFYADAVKGRFTISRDNSKNTLYLQM NSLRAEDTAVYYCAREQLWFGQDAFDIWGQGTLVTVSS 207 VL QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGT APKLLIYGNSNRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYY CQSYDSSLSASVFGGGTKLTVLG 208 003-F10 VH-CDR1 FSDAWMTWVRQAPG 209 VH-CDR2 SDLSDSGGSTYYADSVKGR 210 VH-CDR3 GRLAAGGPVDY 211 VL-CDR1 CTGSSSNIGAGYDVH 212 VL-CDR2 SNNQRPS 213 VL-CDR3 CSVWDDSLNSWV 214 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSDAWMTWVRQAPG KGLEWVSDLSDSGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCGRLAAGGPVDYWGQGTLVTVSS 215 VL QSVLTQPPSASGTPGQRVTISCTGSSSNIGAGYDVHWYQQLP GTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEAD YYCSVWDDSLNSWVFGGGTKLTVLG 216 The sequences in Tables 1 and 2 above are all of human origin and are derived from the n-CoDeR® collection, as explained in detail in Example 1. In some embodiments, the antibody molecules specifically binding to TNFR2 described herein may also comprise one or both of the constant regions (CH and / or CL) listed in Table 3 below. LCLcnn / Lznz / B / Yi Table 3: Región Secuencia SEQ ID NO: CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GK 217 CL QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETT TPSKQSN N KYAASSYLSLTPEQWKSH RSYSCQVTH EGSTVEKTVAPTECS 218 CH AKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPA VLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPTIKPCPPCK CPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCWVDVSEDDPDVQISWFVNNVEV HTAQTQTHREDYNSTLRWSALPIQHQDWMSGKEFKCKVNNKDLPAPIERTISK PKGSVRAPQVYVLPPPEEEMTKKQVTLTCMVTDFMPEDIYVEWTNNGKTELNYK NTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSWHEGLHNHHTTKSFSRTPG K 219 CH AKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPA VLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPTIKPCPPCK CPAPNLLGGPSVFIFPPKIKDVLMISLSPIVTCWVDVSEDDPDVQISWFVNNVEVK 220 CL KATLVCTITDFYPGVVTVDWKVDGTPVTQGM ETT QPSKQSN N KYMASSYLTLTARAWERH SSYSCQVTH EGHTVEKSLSRADCS 221 The first CH sequence (SEQ ID NO: 217) and the first CL sequence (SEQ ID NO: 218) in Table 3 above are of human origin. The second CH (SEQ ID NO: 219) and the third CH (SEQ ID NO: 220) in Table 3 are both from murine IgG2a, with the difference that the third CH sequence (SEQ ID NO: 220) contains an N297A mutation. The second CL sequence (SEQ ID NO: 221) is from the constant region of the murine lambda light chain. These murine sequences are used in the examples for the surrogate antibodies. In some embodiments, the antibody molecule binds to human TNFR2 (hTNFR2). In some embodiments, it is preferred that the agonist antibody molecules bind strongly to human TNFR2, i.e., have a low EC50 value. This is further demonstrated in Example 2. In some embodiments, it is advantageous for the antibody molecule to bind to both hTNFR2 and TNFR2 from Macaca fascicularis (cmTNFR2 or cynoTNFR2). Cross-reactivity with TNFR2 expressed in Macaca fascicularis cells, also known as the crab-eating macaque, can be advantageous, as it allows the antibody molecule to be evaluated in animals without the need for a surrogate antibody, with a particular focus on tolerability. In some embodiments, a surrogate antibody is needed to evaluate the functional activity of an antibody molecule in relevant in vivo mouse models. To ensure comparability between the effect of the antibody molecule in humans and the in vivo results of the surrogate antibody in mice, it is essential to select a functionally equivalent surrogate antibody that has the same in vitro characteristics as the human antibody molecule. In some embodiments, the antibody molecule is not specifically bound to a TNFR2 epitope comprising or consisting of the KCSPG sequence. In some embodiments, the antibody molecule of the present invention or used according to the invention is an antibody molecule that is capable of competing with the specific antibodies provided herein, for example, capable of competing with antibody molecules comprising a VH selected from the group consisting of SEQ ID NO: 7, 15, 23, 31, 39, 47, 55, 63, 71, 79, 87, 95 and 103; and / or a VL selected from the group consisting of SEQ ID NO: 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104, for binding to TNFR2. By able to compete, it is meant that the competing antibody is able to inhibit or otherwise interfere, at least in part, with the binding of an antibody molecule as defined herein to the specific TNFR2 target. For example, such a competing antibody molecule may be able to inhibit the binding of an antibody molecule described herein to TNRF2 by at least about 10%; for example, at least about 20%, or at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or about 100%. Competitive attachment can be determined by methods familiar to mid-level tradespeople, such as the enzyme-linked immunosorbent assay (ELISA). ELISA assays can be used to evaluate antibodies that modify or block the epitope. Additional methods suitable for identifying competing antibodies are disclosed in Antibodies: A Laboratory Manual, Harlow & Lane, which is incorporated herein by reference (e.g., see pages 567–569, 574–576, 583, and 590–612, 1988, CSHL, NY, ISBN 0-87969-314-2). LCLcnn / Lznz / B / Yi In some embodiments, it is of interest to use not the antibody molecule itself, but a nucleotide sequence encoding such an antibody molecule. Therefore, the present invention covers nucleotide sequences encoding antibody molecules against TNFR-2 non-blocking agonists. The non-blocking agonist antibody molecules and nucleotide sequences described above can be used in medicine, and then such an antibody molecule and / or nucleotide sequence can be included in a pharmaceutical composition, as further discussed below. The non-blocking agonist antibody molecules, nucleotide sequences and / or pharmaceutical compositions described above can be used in cancer treatment, as further discussed below. The non-blocking agonist antibody molecules, nucleotide sequences and / or pharmaceutical compositions described above can be used in the treatment of a chronic inflammatory disease, as further discussed below. The non-blocking agonist antibody molecules and / or nucleotide sequences described above may be used in the preparation of a pharmaceutical composition for use in the treatment of cancer. The non-blocking agonist antibody molecules and / or nucleotide sequences described above may be used in the preparation of a pharmaceutical composition for use in the treatment of a chronic inflammatory disease. The non-blocking agonist antibody molecules and / or pharmaceutical compositions described above may be used in a method for the treatment of cancer in a patient, wherein the subject is administered a therapeutically effective amount of an antibody molecule or pharmaceutical composition. The non-blocking agonist antibody molecules and / or pharmaceutical compositions described above may be used in a method for the treatment of a chronic inflammatory disease in a patient, wherein the patient is administered a therapeutically effective amount of an antibody molecule or a pharmaceutical composition. In some contexts related to cancer treatment, the type of cancer is either a solid tumor or a leukemic tumor. A solid tumor is an abnormal mass of tissue that generally does not contain cysts or fluid-filled areas. Solid tumors can be benign (noncancerous) or malignant (cancerous). Malignant solid tumors are referred to here as solid cancer. The different types of solid tumors or cancers are named according to the type of cells that form them. Examples of solid tumors include sarcomas, carcinomas, and lymphomas. LCLcnn / Lznz / E / Yi More specific examples of solid tumor cancers include lung cancer, head and neck cancer, gastric cancer, breast cancer, colorectal cancer, prostate cancer, bladder cancer, ovarian cancer, endometrial cancer, kidney cancer, liver cancer, pancreatic cancer, thyroid cancer, brain cancer, central nervous system cancer, melanoma, neuroblastoma, lymphoma, Wilms tumor, rhabdomyosarcoma, retinoblastoma, and bone cancer. More specific examples of leukemic cancer types include acute lymphocytic leukemia, chronic myeloproliferative disease, acute non-lymphocytic leukemia, B-cell acute lymphocytic leukemia, chronic lymphocytic leukemia, T-cell acute lymphocytic leukemia, non-Hodgkin lymphomas, and chronic lymphoproliferative diseases. In some embodiments, the non-blocking agonist antibody molecules described above can be used in combination with an antibody molecule that specifically binds to a checkpoint inhibitor. Alternatively, the nucleotide sequences discussed above that encode a non-blocking agonist antibody molecule against TNFR2 can be used in combination with an antibody molecule that specifically binds to a checkpoint inhibitor or a co-stimulatory agonist antibody.Examples of antibodies against checkpoint inhibitors include antibodies directed against CTLA4, PD1, PD-L1, VISTA, TIGIT, CD200, CD200R, BTLA, LAG3, TIM3, B7-H3, B7-H4, and B7-H7. Examples of costimulatory agonist antibodies include antibodies directed against OX40, 41BB, OX40L, 41BBL, GITR, ICOS, DR3, DR4, DR5, CD40, CD27, RANK, HVEM, LIGHT, and B7-H6. Alternatively, the non-blocking TNFR2 agonist antibody molecules discussed above can be used in combination with a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor or a costimulatory agonist.Alternatively, the nucleotide sequences analyzed above that encode a non-blocking TNFR2 agonist antibody molecule can be used in combination with a nucleotide sequence that encodes an antibody molecule that specifically binds to a checkpoint inhibitor or a costimulatory agonist. In some such embodiments, the antibody molecule that specifically binds to a checkpoint inhibitor is an anti-PD-1 antibody. Antibodies against PD-1 are thought to block the PD-L1-mediated inhibitory signal, primarily in CD8+ T lymphocytes, thereby enabling an enhanced T-cell-mediated antitumor response. These treatments could synergize with each other. The same is true for other checkpoint inhibitors and costimulatory agonist antibodies. Furthermore, the non-blocking TNFR2 agonist antibody molecules discussed above can be used in combination with other antineoplastic treatments such as chemotherapy (e.g., among others, doxorubicin, paraplatin, cyclophosphamide, paclitaxel, gemcitabine, 5-fluorouracil, docetaxel, vincristine, mitoxantrone, mutamycin, epirubicin and LCLcnn / Lznz / E / Yi methotrexate), small molecule tyrosine kinase or serine / threonine kinase inhibitors (e.g., but not limited to, ibrutinib, imatinib, suntinib, regorafenib, sorafenib, dasatinib, erlotinib, vandetanib, midostaurin, vemurafenib, dabrafenib, palbociclib, ribociclib, trametinib, or alectinib), inhibitors that target growth factor receptors (e.g., but not limited to, drugs that target EGFR / HER1 / ErbB1, EGFR2 / HER2 / ErbB2, EGFR3 / HER3 / ErbB3, VEGFR, PDGFR, HGFR, RET, insulin-like growth factor receptor IGFR, FGFR), antiangiogenic agents (e.g., but not limited to, bevacizumab, everolimus, lenalidomide, thalidomide, zivaflibercept) or radiation. Typically, all of the aforementioned antineoplastic drugs cause the death of cancer cells, leading to the exposure of neoantigens and inflammation.At a time when neoantigens are exposed and there is an entry of inflammatory cells into the tumor, synergistic effects of the antineoplastic drug may occur. A person in a mid-level medical profession will know that medicines can be modified with different additives, for example, to change the rate at which the body absorbs the medicine; and it can be modified in different ways, for example, to allow a particular route of administration to the body. Accordingly, it is included that the non-blocking agonist antibody molecules, nucleotide sequences, plasmids, viruses, and / or cells described herein may be combined with a pharmaceutically acceptable excipient, carrier, diluent, vehicle, and / or adjuvant in a pharmaceutical composition. In this context, the term pharmaceutical composition may be used interchangeably with the terms pharmaceutical preparation, pharmaceutical formulation, therapeutic composition, therapeutic preparation, therapeutic formulation, and therapeutic entity. The pharmaceutical compositions described herein may comprise, or in some embodiments consist of, antibody molecules, nucleotide sequences, plasmids, viruses, or cells. The pharmaceutical compositions described herein may, in some embodiments, comprise or consist of plasmids comprising nucleotide sequences encoding the antibody molecules described above or comprising the nucleotide sequences described above. In some embodiments, the pharmaceutical compositions may comprise nucleotide sequences encoding portions of, or a complete antibody molecule as described herein, integrated into a cell, a viral genome, or a viriome. The pharmaceutical composition may then comprise a cell or a virus as a delivery vehicle for an antibody of the invention (or a delivery vehicle for a sequence). LCLcnn / Lznz / B / Yi of nucleotides encoding an antibody of the invention). For example, in one embodiment, the virus may be in the form of a therapeutic oncolytic virus comprising nucleotide sequences encoding at least one of the antibody molecules described herein. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding a full-length human IgG antibody. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding an scFv, Fab, or F(ab')2 antibody molecule. As described in the appended claims, in some embodiments, the invention relates to a virus comprising a nucleotide sequence of the invention or a plasmid of the invention. Preferably, the virus is an oncolytic virus, such as a therapeutic oncolytic virus. Such viruses are known to persons of intermediate skill in medicine and virology. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding an amino acid sequence that has at least 80% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises an amino acid sequence that has at least 85% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises an amino acid sequence that has at least 90% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises an amino acid sequence that has at least 95% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 7 and ID NO: 8. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 15 and ID NO: 16. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 23 and ID NO: 24. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 31 and ID NO: 32. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 39 and ID NO: 40. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 47 and ID NO: 48. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 55 and ID NO: 56.In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 63 and ID NO: 64. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 71 and ID NO: 72. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 79 e. LCLcnn / Lznz / E / Yi ID NO: 80. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 87 and ID NO: 88. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 95 and ID NO: 96. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding SEQ ID NO: 103 and ID NO: 104. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding amino acid sequences that have at least 80% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding amino acid sequences that have at least 85% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding amino acid sequences that have at least 90% identity with a sequence specified in Table 1 above. In some embodiments, such an oncolytic virus comprises nucleotide sequences encoding amino acid sequences that have at least 95% identity with a sequence specified in Table 1 above. As an example, a nucleotide sequence that codes for antibody 001-F02 could be as shown in Table 4. Table 4: eiemolo of nucleotide sequences encoding antibody 001-F02 (the parts of the sequences that are underlined in the table encode the VH and VL sequences, respectively, of 001-F02). LCLcnn / Lznz / B / Yi Codifica Secuencia SEQ ID NO: 001-F02 VH GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTG 222 AGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTACATGAGCTGGGT CCGCCAGGCTCCCGGGAAGGGGCTGGAGTGGGTGGCCAACATAAACACAGACGG TAGTGAAAAATACTATCTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACA ATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACTGC CGTGTATTACTGTGCGAGAGAGGAGTACGGTGLI 1 1 1GATATCTGGGGCCAAGGT ACACTGGTCACCGTGAGCTCAGCCTCCACCAAGGGCCCATCGG1C1 1CCCCCTGG CACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG CGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTG ACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTC AG1C1 1LC1L1 1CCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG AGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAA CTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGA Codifica Secuencia SEQ ID NO: 001-F02 VH GCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGAC TGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCC CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGC CTGGTCAAAGGG1 1C1ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACrCCGACGGCTCCTT CrTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCT CTCCCTGTCTCCGGGTAAATGA 222 001-F02 VL CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCA 223 CCATG1G1 1G1 1L1GGAAGCAGCTCCAACATCGGAAGTAATACTGTAAACTGGTAT CAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATGACAATAATAAGCGACC CTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTG GCCATCAGTGGGCrrCCGGTCCGAGGATGAGGCTGATTATTACTGCCAGTCCTTTG ACAGAGGGCTGAGTGGCTCGATTGTATTCGGCGGAGGAACCAAGCTGACGGTCCT AGGTCAGCCCAAGGCTGCCCCCTCGGTCAL1 Ll G1 1CCCGCCCTCCTCTGAGGAG CTTCAAGCCAACAAGGCCACACTGGTGTGTCTCATAAGTGAC1 1C1ACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGAGTGGAGA CCACCACACCCTCCAAACAAAGCAACAGTACGCGGCCAGCAGCTATCTGAGC CTGACGCCTGAGCAGTGGAAGTCCCACAAGCTACAGCTGCCAGGTCACGCATG AAGGGAGCACCGTGGAGAGACAGTGGCCCCTACAGAATGTTCATGA LCLcnn / Lznz / B / Yi Some oncolytic viruses have the capacity to host DNA insertions large enough to accommodate the integration of full-length human antibody sequences. Attenuated vaccinia viruses and herpes simplex viruses are examples of therapeutic oncolytic viruses whose genomes are large enough to allow the integration of full-length IgG antibody sequences (Chan, WM et al. 2014 Annu Rev Virol 1(1): 119-141; Bommareddy, PK, et al. 2018 Nat Rev Immunol 18(8): 498-513). Full-length IgG antibodies have been successfully integrated into the oncolytic vaccinia virus, resulting in the expression and extracellular release (production) of full-length IgG antibodies following infection of virus-susceptible host cells, such as cancer cells (Kleinpeter, P., et al. 2016 Oncoimmunology 5(10): el220467).Adenoviruses can also be genetically engineered to encode full-length IgG antibodies that are functionally produced and secreted following cell infection (Marino, N., et al 2017 J Clin Invest 123(6): 2447-2463). The invention also includes pharmaceutical compositions comprising a virus, such as an oncolytic virus as discussed above, and a pharmaceutically acceptable diluent, vehicle and / or adjuvant. In some embodiments, the pharmaceutical composition may be in the form of a CAR T lymphocyte, which carries parts or the complete antibody sequences described herein as part of the sequence encoding its chimeric antigen T lymphocyte receptor. The invention also encompasses pharmaceutical compositions comprising a CAR T lymphocyte as discussed above and a pharmaceutically acceptable diluent, vehicle and / or adjuvant. The invention also comprises other therapeutic modalities or drug forms, such as antibody-drug conjugates, fusion proteins, etc., and a pharmaceutical composition comprising such therapeutic modalities. The antibody molecules, nucleotide sequences, plasmids, viruses, cells and / or pharmaceutical compositions described herein may be suitable for parenteral administration, including sterile aqueous and / or non-aqueous injection solutions that may contain antioxidants, and / or buffers, and / or bacteriostatics and / or solutes that make the formulation isotonic with the blood of the intended recipient; and / or sterile aqueous and / or non-aqueous suspensions that may include suspending agents and / or thickening agents.The antibody molecules, nucleotide sequences, plasmids, cells and / or pharmaceutical compositions described herein may be presented in unit-dose or multi-dose containers, e.g., sealed ampoules and vials, and may be stored in a freeze-dried (i.e., lyophilized) condition requiring only the addition of the sterile liquid carrier, e.g., water for injection, immediately prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powders and / or granules and / or tablets of the type described above. For parenteral administration to human patients, the daily dose level of the anti-TNFR2 antibody molecule will typically be 1 mg / kg of the patient's body weight to 20 mg / kg, or in some cases even up to 100 mg / kg, administered in single or divided doses. Lower doses may be used in special circumstances, for example, in combination with prolonged administration. In any case, the physician will determine the actual dose that will be most appropriate for any individual patient, and this will vary with age, weight, and the patient's individual response. The above dosages are examples of the average case. Of course, there may be individual cases where higher or lower dose ranges are required, and these are within the scope of the present invention. Generally, a pharmaceutical composition (or drug) described herein comprising an antibody molecule shall contain the antiTNFR2 antibody molecule at a concentration of between approximately 2 mg / mL and 150 mg / mL or between approximately 2 mg / mL and 200 mg / mL. Generally, in humans, oral or parenteral administration of the antibody molecules, nucleotide sequences, plasmids, viruses, cells, and / or pharmaceutical compositions described herein is the preferred route, as it is the most convenient. For veterinary use, the antibody molecules, nucleotide sequences, plasmids, viruses, cells, and / or The pharmaceutical compositions described herein are administered as a suitably acceptable formulation in accordance with normal veterinary practice, and the veterinary surgeon will determine the dosage regimen and route of administration most appropriate for a particular animal. The present invention provides a pharmaceutical formulation comprising a quantity of an antibody molecule, nucleotide sequence, plasmid, virus, and / or cell of the invention effective for treating various conditions (as described above and below). Preferably, the antibody molecules, nucleotide sequences, plasmids, viruses, cells, and / or pharmaceutical compositions described herein are adapted for administration by a route selected from the group comprising: intravenous (IV); intratumoral (IM); subcutaneous (SC); or intratumoral. The present invention also includes antibody molecules, nucleotide sequences, plasmids, viruses, cells and / or pharmaceutical compositions described herein comprising pharmaceutically acceptable acid or basic addition salts of the target-binding molecules or parts of the present invention.The acids used to prepare pharmaceutically acceptable acid addition salts of the aforementioned basic compounds useful in this invention are those that form non-toxic acid addition salts, i.e., salts containing pharmaceutically acceptable anions, such as hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succinate, maleate, fumarate, gluconate, sucrate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate [i.e., 1,T-methylene-bis-(2-hydroxy-3-naphthoate)], among others. Pharmaceutically acceptable basic addition salts may also be used to produce pharmaceutically acceptable salt forms of the agents according to the present invention.The chemical bases that can be used as reagents to prepare pharmaceutically acceptable basic salts of the present agents, which are acidic in nature, are those that form non-toxic basic salts with such compounds. Such non-toxic basic salts include, but are not limited to, those derived from pharmaceutically acceptable cations such as alkali metal cations (e.g., potassium and sodium) and alkaline earth metal cations (e.g., calcium and magnesium), water-soluble ammonium or amine addition salts such as N-methylglucamine (meglumine) and lower alkanolammonium, and other pharmaceutically acceptable basic salts of organic amines. The antibody molecules, nucleotide sequences, plasmids, viruses, and / or cells described herein may be lyophilized for storage and reconstituted in a suitable carrier prior to use.Any suitable freeze-drying method (e.g., spray drying, cake drying) and / or reconstitution techniques may be used. LCLcnn / Lznz / E / Yi Mid-level practitioners will appreciate that lyophilization and reconstitution can result in varying degrees of antibody activity loss (e.g., with conventional immunoglobulins, IgM antibodies tend to have a greater loss of activity than IgG antibodies) and that usage levels may need to be adjusted incrementally to compensate. In one embodiment, the fixative portion of the lyophilized (freeze-dried) polypeptide loses no more than about 20%, or no more than about 25%, or no more than about 30%, or no more than about 35%, or no more than about 40%, or no more than about 45%, or no more than about 50% of its activity (prior to lyophilization) upon rehydration. The anti-TNFR2 antibody molecules, nucleotide sequences, and pharmaceutical compositions described herein may be used in the treatment of cancer in a subject. Herein, the terms subject and patient are used interchangeably. Patient (or subject), as the term is used herein, refers to an animal, including a human, that has been diagnosed with cancer and / or exhibits symptoms of a specific disease. In some forms of realization, the patient (or subject) is an animal, or even a human being, who has been diagnosed with cancer. In some embodiments, the patient (or subject) is an animal, or even a human, diagnosed with and / or exhibiting symptoms of a chronic inflammatory disease. Chronic inflammatory diseases as used herein include autoimmune diseases. As described above, several different immune cells can express TNFR2, and the relative levels of expression can vary depending on the disease and context. Regulatory T cells, for example, are known to express elevated levels of TNFR2, and these can be expanded by TNFR2 agonists. Regulatory T cells constitute a subpopulation of T cells capable of suppressing other immune cells in both normal and pathological immune environments and are considered critical for preventing autoimmune attacks on self-tissues.Therefore, stimulating the activity of regulatory T lymphocytes could be very important in the treatment of autoimmune disorders (Sharabi et al. Regulatory T cells in the treatment of disease. Nat Rev Drug Discov. October 12, 2018). Examples of chronic inflammatory diseases in addition to autoimmune disorders include osteoarthritis and celiac disease. Examples of autoimmune disorders include rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus, systemic lupus erythematosus (SLE), psoriasis, inflammatory bowel disease (IBD), and myasthenia gravis (MG). In some embodiments, the patient (or subject) is a patient with high TNFR2 expression in diseased tissue. In this context, high expression means a higher level LCLcnn / Lznz / B / Yi shows high TNFR2 expression compared to the corresponding healthy tissue. Typically, the healthy tissue used for such comparison is a reference (or reference standard) tissue collected from one or more healthy individuals. The expression level can be measured using standard techniques such as immunohistochemistry (IHC), fluorescence-activated cell separation (FACS), or mRNA expression measurements. It is specified that the patient may be a mammal or a non-mammal. Preferably, the mammalian patient is a human, a horse, a cow, a sheep, a pig, a camel, a dog, or a cat. Most preferably, the mammalian patient is a human. Exhibiting symptoms of cancer includes the subject showing a symptom of cancer and / or a cancer diagnostic marker, and / or the cancer symptom and / or a cancer diagnostic marker can be measured and / or evaluated and / or quantified. It would be obvious to a person of mid-level medical skill what the symptoms of cancer and the cancer diagnostic markers would be, and how to measure and / or evaluate and / or quantify whether there is a reduction or an increase in the severity of cancer symptoms, or a reduction or an increase in cancer diagnostic markers; as well as how those cancer symptoms and / or cancer diagnostic markers could be used to make a prognosis for cancer. Cancer treatments are often administered as a treatment cycle, meaning the therapeutic agent is given over a period of time. The length of the treatment cycle depends on several factors, which may include the type of therapeutic agent being given, the type of cancer being treated, the severity of the cancer, and the patient's age and health, among other reasons. During treatment, this includes the patient currently receiving a course of treatment, and / or receiving a therapeutic agent, and / or receiving a course of a therapeutic agent. In some embodiments, the cancer to be treated according to the present invention is a solid tumor. Each of the cancer types described above is well-known, and the symptoms, diagnostic markers, and therapeutic agents used to treat them are documented. Therefore, these symptoms, diagnostic markers, and therapeutic agents would be familiar to mid-level medical professionals. The clinical definitions of diagnosis, prognosis, and progression for many types of cancer depend on certain classifications known as staging. These staging systems compile various cancer diagnostic markers and symptoms to provide a summary of the diagnosis and / or prognosis. LCLcnn / Lznz / B / Yi cancer progression. The mid-level oncology practitioner will know how to assess the diagnosis and / or prognosis and / or progression of cancer using a staging system, and what cancer diagnostic markers and symptoms should be used to do so. Cancer staging includes the Raí staging, which includes stage 0, stage I, stage II, stage III and stage IV, and / or the Binet staging, which includes stage A, stage B and stage C, and / or the Ann Arbor staging, which includes stage I, stage II, stage III and stage IV. Cancer is known to cause abnormalities in cell morphology. These abnormalities often occur reproducibly in certain types of cancer, meaning that examining these morphological changes (also known as histological examination) can be used in cancer diagnosis or prognosis. Techniques for visualizing samples to examine cell morphology and preparing samples for visualization are well-known; for example, optical microscopy or confocal microscopy. Histological examination includes the presence of small, mature lymphocytes, and / or the presence of small, mature lymphocytes with a narrow border of cytoplasm, the presence of small, mature lymphocytes with a dense nucleus lacking discernible nucleoli, and / or the presence of small, mature lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli, and / or the presence of atypical cells and / or cleaved cells and / or prolymphocytes. It is known that cancer results from mutations in a cell's DNA, which can lead to the cell evading cell death or to uncontrolled proliferation. Therefore, examining these mutations (also known as cytogenetic testing) can be a useful tool for evaluating the diagnosis and / or prognosis of a type of cancer. An example of this is the deletion of the chromosomal location 13q14.1, which is characteristic of chronic lymphocytic leukemia. Techniques for examining mutations in cells are well-known; for example, fluorescence in situ hybridization (FISH). Cytogenetic testing involves examining the DNA in a cell, and specifically the chromosomes. Cytogenetic testing can be used to identify DNA changes that may be associated with resistant and / or recurrent cancer. These may include: deletions on the long arm of chromosome 13, and / or deletion of chromosomal location 13q14.1, and / or trisomy of chromosome 12, and / or deletions on the long arm of chromosome 12, and / or deletions on the long arm of chromosome 11, and / or deletion of 11q, and / or deletion of 6q, and / or deletions on the short arm of chromosome 17, and / or deletion of 17p, and / or the t(11:14) translocation, and / or the LCLcnn / Lznz / E / Yi translocation (ql3:q32), and / or rearrangements of antigen receptor genes, and / or rearrangements of BCL2, and / or rearrangements of BCL6, and / or translocations t(14:18), and / or translocations t(ll: 14), and / or translocations (ql3: q32), and / or translocations (3:v), and / or translocations (8:14), and / or translocations (8:v), and / or translocations t(ll: 14) and (ql3:q32). It is known that cancer patients exhibit certain physical symptoms, which are often a result of the cancer's burden on the body. These symptoms often recur in the same type of cancer and, therefore, can be characteristic of the diagnosis, prognosis, and / or progression of the disease. A mid-level medical practitioner will understand which physical symptoms are associated with which cancer types and how evaluating these physical systems can correlate with the diagnosis, prognosis, and / or progression of the disease. Physical symptoms include hepatomegaly and / or splenomegaly. BRIEF DESCRIPTION OF THE DRAWINGS The examples below refer to the following figures: Figures 1A to 1E demonstrate that the antibodies of the invention bind to TNFR2. Figure 1A to 1D: It was demonstrated by ELISA that the human antibodies bind to the human TNFR2 protein in a dose-dependent manner, resulting in different EC50 values. Figure 1E: Murine antibodies 3-F10 and 5-A05 bind to mTNFR2 with similar affinity. Figures 2A to 2E demonstrate the binding of TNFR2-specific n-CoDeR® antibodies to activated CD4+ T lymphocytes in vitro. Human blood-derived CD4+ T lymphocytes (Figures 2A to 2D) and mouse splenic CD4+ T lymphocytes (Figure 2E) were activated with CD3 / CD28 and IL-2 Dynabeads®. The affinity of TNFR2-specific n-CoDeR® antibodies to activated lymphocytes was analyzed by FACS at concentrations ranging from 0.002267 nM (human) to 0.00003–133 nM (mouse). The curves show MFI after subtracting the isotype control background (Figure 2A (full and partial blockers), Figure 2B (partial blockers), Figure 2C and 2D (non-blockers), Figure 2E (mouse surrogate full blocker (3F10) and non-blocker (5-A05)). While human TNFR2 antibodies bind with different affinities to activated CD4+ T lymphocytes in vitro (EC50 values ​​ranging from 0.59 to 53 nM), mouse TNFR2 antibodies bind with similar affinity (EC50 values ​​ranging from 0.072 to 0.11 nM). Figures 3A and 3B show that n-CoDeR® antibodies against TNFR2 bind specifically to TNFR2. Human blood-derived CD4+ T lymphocytes were activated (Figure LCLcnn / Lznz / E / Yi 3A) and mouse splenic CD4+ T lymphocytes (Figure 3B) for 3 days with CD3 / CD28 activation microspheres and recombinant IL-2. The in vitro activated lymphocytes were blocked with a polyclonal antibody against TNFR2 (gray line) or left in PBS (black line) for 30 min before staining with a suboptimal concentration of different n-CoDeR® antibodies against TNFR2 or isotype control (dashed line) for 15 min. The lymphocytes were then washed and incubated with an APC-conjugated secondary antibody for 30 min before analysis by flow cytometry. The binding of all antibodies could be blocked by the polyclonal antibody against TNFR2; therefore, n-CoDeR® antibodies against TNFR2 (human and mouse) are shown to be specific against TNFR2. Figure 4 shows the cross-reactivity of specific n-CoDeR® antibodies against human TNFR2 compared to Macaca fascicuaris. CD4+ T lymphocytes were isolated from Macaca fascicuaris blood and stimulated with PMA and ionomycin. After 2 days, the lymphocytes were labeled with 0.1, 1, or 10 pg / mL of n-CoDeR® antibodies specific against TNFR2 or isotype control, followed by incubation with an APC-conjugated human a-antibody. The lymphocytes were analyzed by flow cytometry. The figure shows the percentages of TNFR2+ T lymphocytes for the individual antibodies relative to the isotype control. Results are the mean and standard deviation of 2–3 individual experiments. Most antibodies against TNFR2 show cross-reactive attachment to Macaca fascicuaris lymphocytes. Figures 5A and 5B. Activated lymphocytes were blocked with 40 pg / mL of MR2-1 antibody (Figure 5A, black bars) or left in PBS (Figure 5A, gray bars) for 30 min, then n-CoDeR® antibodies specific against TNFR2 / polyclonal TNFR2 (pTNFR2) were added, and the lymphocytes were incubated for 15 min. The percentage of n-CoDeR® antibodies against TNFR2 bound was analyzed by FACS after incubation with APC-conjugated secondary antibodies. In Figure 5B, activated CD4+ T lymphocytes were blocked with 40 pg / mL of n-CoDeR® antibodies specific against TNFR2 / pTNFR2 (black bars) or left in PBS (gray bar) and then incubated for 15 min with PE-conjugated MR2-1 antibody. Next, the lymphocytes were analyzed using FACS. The MR2-1 antibody did not interfere with the binding of TNFR2-specific n-CoDeR® antibodies, and the n-CoDeR® antibodies did not affect the binding of MR2-1 to activated lymphocytes, showing that all n-CoDeR® antibodies bind to domains of the TNFR2 protein other than the MR2-1 antibody. This demonstrates that TNFR2-specific n-CoDeR® antibodies bind to other epitopes of the TNFR2 protein in addition to the MR2-1 antibody. LCLcnn / Lznz / E / Yi of clone MR2-1 against TNFR2. Human blood-derived CD4+ T lymphocytes were stimulated with CD3 / CD28 activation microspheres and rhIL-2 for 2–3 days. Activated lymphocytes were blocked with 40 pg / mL of MR2-1 antibody (Figure 5A, black bars) or left in PBS (Figure 5A, gray bars) for 30 min, then n-CoDeR® antibodies specific against TNFR2 / polyclonal TNFR2 (pTNFR2) were added, and the lymphocytes were incubated for 15 min. The percentage of n-CoDeR® antibodies against TNFR2 bound was analyzed by FACS after incubation with APC-conjugated secondary antibodies. In Figure 5B, activated CD4+ T lymphocytes were blocked with 40 pg / mL of n-CoDeR® antibodies specific against TNFR2 / pTNFR2 (black bars) or left with PBS (gray bar) and then incubated for 15 min with PE-conjugated MR2-1 antibody. The lymphocytes were then analyzed by FACS. The MR2-1 antibody did not interfere with the binding of TNFR2-specific n-CoDeR® antibodies, and the n-CoDeR® antibodies did not affect the binding of MR2-1 to activated lymphocytes, showing that all n-CoDeR® antibodies bind to other domains of the TNFR2 protein besides the MR2-1 antibody. Figures 6A and 6E show the ligand-blocking antibody data. Ligand-blocking ELISAs were performed using hTNFRII-specific n-CoDeR® mAbs to evaluate ligand-blocking characteristics. Figure 6A: All antibodies were incubated at 10 pg / mL. Subsequently, all antibodies that reduced the signal achieved with the isotype control by more than 50% (indicated by the dashed line) were measured to further explore ligand-blocking potential. Figure 6B shows complete-blocking mAbs, Figures 6C and 6D show partial-blocking mAbs, and Figure 6E shows weak-blocking mAbs. All other mAbs are considered non-blocking mAbs. Figures 7A to 7E show the ligand-blocking antibody data. Ligand-blocking ELISAs were performed using mTNFRII-specific n-CoDeR® mAbs to evaluate ligand-blocking characteristics. Figure 7A: All antibodies were incubated at 10 pg / mL. Subsequently, all antibodies that reduced the signal achieved with the isotype control by more than 50% (indicated by the dashed line) were measured to further explore ligand-blocking potential. Figure 7B shows complete-blocking mAbs, Figures 7C and 7D show partial-blocking mAbs, and Figure 7E shows weak-blocking mAbs. All other mAbs are considered non-blocking mAbs. Figures 8A to 8D show that TNFR2-specific n-CoDeR® antibodies, which are non-blocking agonists but not antagonists, enhance IFN-γ production in IL-2 and IL-12-stimulated NK cells. Figure 8A: Human blood-derived NK cells were stimulated with 20 ng / mL of rhIL-2 and 20 ng / mL of rhIL-12 with the addition of 10 pg / mL of LCLcnn / Lznz / B / Yi TNFR2-specific n-CoDeR® antibodies, isotype control, or 100 ng / mL rhTNF-α were administered for 24 h. IFN-γ levels in the culture supernatants were measured using MSD. The IFN-γ level was normalized to the isotype control and is shown in Figure 8A. Human antibodies with an EC50 value greater than 25 nM for in vitro activated CD4+ T lymphocytes were excluded from the analysis. Human NK cells also produce TNF-α in these cultures (see Figure 8D below). IFN-γ results are the mean value from 3 donors in 2 independent experiments. The results show that non-blocking TNFR2 antibodies are agonists and enhance IFN-γ production from cytokine-stimulated NK cells, while blocking antibodies are antagonists and decrease IFN-γ production by NK cells.Furthermore, Figures 8B to 8D show that agonist antibodies have intrinsic agonist activity, even in the absence of measurable TNF-α ligand. As shown in Figure 8B, the addition of blocking antibody against TNF-α reduces the amount of IFN-γ released, but the ratio over an isotype control (Figure 8C) is still maintained even in the total absence of measurable TNF-α in the supernatant (Figure 8D). Figure 8D shows the mean TNF-α levels in two donors in the presence or absence of neutralizing antibodies against TNF-α. Figures 9A to 9B show that non-blocking, agonist-type, non-blocking n-CoDeR® antibodies against TNFR2 activate the memory CD4+ T cell population, as indicated by an increase in the proportion of CD25+ T cells. Human blood-derived CD4+ T cells (Figure 9A) and mouse splenic CD4+ T cells (Figure 9B) were activated with TNFR2-type n-CoDeR® antibodies and recombinant IL-2, isotype control, or recombinant TNF-α. After 3 days of culture, the cells were stained for CD25 and CD45RO (human) / CD44 and CD62L (mouse) and analyzed by flow cytometry. The results show the percentage of lymphocytes expressing CD25 in the memory population (CD45RO+ (human) / CD44+CD62L (mouse) lymphocytes) over the percentage of CD25+ lymphocytes recovered in isotype-controlled cultures.The results are the mean value and SEM of 7 donors (Figure 9A, humans) and 3 mice (in 2 independent experiments) (Figure 9B). In human and mouse cultures, non-blocking antibodies against TNFR2 induced the percentage of CD25+ memory T lymphocytes, while blocking antibodies had no such effect on the memory population. In both human (Figure 9A) and mouse (Figure 9B) cultures, the addition of exogenous TNF-α increased the CD25+ memory T lymphocyte population. *=p<0.05 as calculated by one-way ANOVA. Figures 10A to 10D show that the anti-TNFR2 mAb modulates the suppressor function of myeloid-derived suppressor cells (MDSCs). For Figures 10A and 10B, the MDSCs were pre-incubated with human anti-TNFR2 mAb for 30 min. Without washing the cells, LCLcnn / Lznz / B / Yi were then incubated with CFSE-labeled CD3+ T lymphocytes in the presence of CD3 / CD28 Dynabeads®. Figure 10A: The percentage of activated CD25+ T lymphocytes was determined after 3 days using FACS. To normalize between assays, the isotype control background was subtracted from all data points. The figure shows a summary of 6 different donors in 3 independent experiments at an MDSC-to-T lymphocyte ratio of 1:4. Figure 10B: The amount of cytokines secreted in the supernatant was assessed using MSD, and the ratio of IFN-γ to IL-10 release was calculated relative to the isotype control. Data were pooled from supernatants obtained from experiments with 5 different donors. For Figure 10C, CD11b+ myeloid cells were isolated from a mouse CT26 tumor and pre-incubated with mouse anti-TNFR2 mAb for 30 min. Titration numbers of myeloid cells were co-cultured with CFSE-labeled CD3+ T lymphocytes purified from untreated Balb / C spleens. The cells were stimulated with CD3 / CD28 Dynabeads® for 3 days, and the percentage of proliferating CFSE cells was then analyzed by FACS (n=4 independent experiments). Only the agonist / non-blocker anti-TNFR2 mAb was shown to reverse the suppressive function of MDSCs in T lymphocyte / MDSC co-culture assays. For Figure 10D, MDSCs were pre-incubated for 30 min with two different human anti-TNFR2 mAbs (one blocking = 1H10) and one non-blocking (=1FO2) in 3 different isotypes, including the Fe-defective format where the position of amino acid 297 has been changed, resulting in loss of glycosylation and, therefore, decreased binding to FcyR (referred to herein as N297Q). Without washing the cells, the MDSC titration numbers were then incubated with CFSE-labeled CD3+ T lymphocytes in the presence of CD3 / CD28 Dynabeads®, and the percentage of activated CD25+ T lymphocytes was determined after 3 days by FACS. To normalize between different assays, the isotype control background was subtracted from all data points. The figure shows that the agonist activity of the non-blocking 1-F02 antibody is independent of antibody isotype and FcyR binding.The figure shows a summary of 4 different donors in 2 independent experiments at an MDSC to T lymphocyte ratio of 1:4. Figures 11A to 11B. For Figure 11A, Balb / c mice were injected subcutaneously with 1x106 CT26 lymphocytes. After 8 days, with a mean tumor size of 3x3 mm, the mice were treated twice weekly with 10 mg / kg of the ip antibody as shown in the figures. Tumors were measured twice weekly until they reached a diameter of 15 mm, after which the mice were euthanized. The top figure shows tumor growth in isotype-controlled treated mice; the two figures below, in the left panel, show the antagonist ligand-blocking antibody. LCLcnn / Lznz / B / Yi (center figure) and the non-blocking agonist ligand antibody (bottom figure) in the FcyR-deficient Ig format. The middle panel shows the same antibodies in murine IgG2a format, which primarily target activating FcyRs, and the right panel shows the antibodies in murine IgG1 format, which primarily interact with the inhibitory FcyRIIb. For Figure 11B, surviving mice were followed for 70 days. As seen in the figures, the non-blocking agonist antibody is most effective as a tumor treatment in an IgG1 format that primarily interacts with the inhibitory FcyR. Furthermore, the agonist antibody has FcyR-independent antitumor effects, as observed with the N297A format.On the other hand, the blocking antagonist antibody is more effective as a treatment against the tumor in an IgG2a format that interacts primarily with FcyR activators and has no effect in a format with defective FcyR binding. ***=p<0.001 compared to the isotype control as calculated by the log-rank Mantel-Cox test. Figures 12A to 12E. C57 / BL6 mice were injected subcutaneously with 1x106 MC38 cells. With a mean tumor size of 3x3 mm, the mice were treated twice weekly with 10 mg / kg of ip antibody as indicated in the figures. The figure shows the tumor growth curves for individual mice. Figure 12A: isotype control, Figure 12B: antibody directed against PD-1, Figure 12C: 5A05 antibody (surrogate antibody, non-ligand blocker and agonist), Figure 12D: combination of 5A05 and PD-1. Tumors were measured twice weekly until they reached a diameter of 15 mm, after which the mice were euthanized. Figure 12E shows the survival curves of the four different treatment groups, *=p<0.05, ***=p<0.001 compared to the isotype control as calculated by the log-rank Mantel-Cox test. Figure 13 shows that ligand-blocking agonist antibodies are effective as an antitumor treatment in combination with anti-PD-L1. C57 / BL6 mice were injected subcutaneously with 1x106 MC38 cells. With a mean tumor size of 5x5 mm, the mice were treated twice with either isotype control antibody or 5A05 (days 1 and 4), or for four consecutive days with anti-PD-L1 followed by a fifth injection two days later (a total of five injections on days 1, 2, 3, 4, and 7), or a combination of both. All antibodies were administered at 10 mg / kg ip. Figure 13 shows the mean tumor growth ± SEM, n=10 / group. *=p<0.05, ***=p<0.001 as calculated by one-way ANOVA. Figures 14A to 14C. C57 / BL6 mice were injected subcutaneously with 1x106 B lymphocytes. After 3 days, the mice were treated twice weekly with 10 mg / kg of ip antibody. Tumors were measured twice weekly until they reached a diameter of 15 mm, after which the mice were euthanized. Figure 14A: isotype control, Figure 14B: 5A05 antibody (surrogate antibody, non-ligand blocker and agonist). LCLcnn / Lznz / B / Yi Figure 14C shows survival curves for the two different treatment groups. *=p<0.05 compared to isotype control as calculated using the log-rank Mantel-Cox test. Figures 15A to 15D. The 5A05 ligand non-blocking agonist surrogate antibody alters the composition of immune cells in tumors. Mice were inoculated with CT26 tumor cells as described and injected with antibodies as indicated once the tumors reached a size of approximately 7 x 7 mm. After 3 injections, on day 8 post-treatment, the mice were euthanized and the tumors were collected. Single-cell tumor suspensions were analyzed for immune cell content by FACS. FIG. 15A. The 5A05 ligand non-blocking agonist surrogate antibody results in decreased Tregs, and 15B results in the entry or expansion of CD8+ T lymphocytes. This leads to a change in the Treg / CD8+ T lymphocyte ratio as shown in C.Figure 15D shows that not only T lymphocytes but also myeloid cells—here, the number of tumor-associated macrophages (TAMs, defined as CD11b+ but Ly6G and Ly6C negative)—are significantly reduced. The 3F10 ligand-blocking antagonist surrogate antibody also modulates the number of TAMs, but it remains significantly different from 5A05. Figure 16. NOG mice were injected intravenously with 15–20 × 10⁶ PBMC cells. After 10–12 days, the spleens of the mice were harvested, a single-cell suspension was prepared, and TNFR2 expression was assessed using FACS. Previously, TNFR2 expression had been assessed in T lymphocytes extracted from blood and tumor samples from 3 or 9 cancer patients, respectively. As shown in the figure, TNFR2 expression in TTreg and CD8+ T lymphocytes is highly comparable between human T lymphocytes cultured and activated in vivo in NOG mice and T lymphocytes from human tumors. Figures 17A to 17B. NOG mice were injected intravenously with 15–20 × 10⁶ PBMC cells. After 10–12 days, the spleens of the mice were harvested, a single-cell suspension was prepared, and the cells were analyzed by FACS. Figure 17A shows the mean percentage of stained Tregs, defined as CD45+CD3+CD4+CD25+CD12710V7ne9, of the total number of cells in the spleen. Figure 17B shows the mean percentage of T lymphocytes (CD3+) of the total number of cells in the spleen. As shown in Figure 17B, the non-blocking agonist antibody 1F02 increases the number of Tregs (expressing the highest levels of TNFR2) as well as the total number of T lymphocytes in this model. For comparison, the 1H10 ligand-blocking antagonist antibody does not have this effect. Figures 18A to 18C. The release of IFN-γ induced by various specific antibodies against TNFR2 was measured in three different in vitro systems. As positive controlsAn anti-CD3 antibody (OKT3 or Muromonab-CD3), an anti-CD52 antibody (alemtuzumab), and an anti-CD28 antibody were used. The isotype control was used as a negative control. Each dot represents PBMCs from a human donor. Figure 18A shows the results of high-density cell cultures where PBMCs were cultured at 1 x 107 cells / mL. After 48 h, 10 pg / mL of antibody was added, and the cells were incubated for 24 h. As seen in the figure, both alemtuzumab and OKT3 induced a significant release of IFN-γ, but neither of the TNFR2-specific antibodies did. Figure 18B shows in vitro solid-phase cultures performed by coating the cavities of a 96-cavity plate with antibodies before adding the PBMCs. Again, both alemtuzumab and OKT3 induced a significant release of IFN-γ along with some of the specific antibodies against TNFR2, particularly in one of the donors.Figure 18C shows whole blood stimulation with antibody, and here alemtuzumab induced a significant release of IFN-γ, but not any of the specific antibodies against TNFR2. Figures 19A to 19C: NOG mice were injected intravenously with 25-x106 PBMC cells. After 14 days, when the mice's blood was shown to consist of approximately 40% human T lymphocytes, the mice were treated with 10 pg of antibody. Body temperature was measured 1 h post-injection (Figure 19A). The experiment was terminated 5 h post-injection, and blood was analyzed for IFN-γ (Figure 19B) or TNF-α (Figure 19C) content. ****=p<0.0001 and **=p<0.01 as calculated by one-way ANOVA. Figures 20A to 20F show binding to TNFR2 variants lacking individual domains. Antibody binding to TNFR2 variants expressed in HEK cells was assessed using flow cytometry. The absence of domains 1 and 2 does not significantly affect binding (Figures 20A and 20B), whereas the absence of domain 3 and partially of domain 4 completely abolishes the interaction between the antibody and TNFR2 (Figures 20C and 20D). Similarly, the absence of domain 1+3 completely prevents binding of all antibodies (except 1F06) (Figure 20E), while the absence of domain 2+4 completely abolishes binding of the agonist antibodies (1F02, 1F06, 4E08) and significantly reduces binding for the antagonist antibodies (1H10, 4H02, 5B08) as well (Figure 20F). Dark gray indicates positive control and white indicates negative control antibody. Figure 21 shows a comparison of the amino acid sequences of human (H-D3) and mouse (M-D3) domain 3 of TNFR2. Similar amino acids are highlighted in white, while differences are highlighted in gray. The following five sequences represent the five different constructs against which the antibodies are evaluated. Sequence exchanges between human and mouse are underlined, while the unmarked sequence is entirely human. Domains 1, 2, and 4 are human and contain no substitutions or mutations. LCLcnn / Lznz / B / Yi Figure 22. Binding to wild-type human and mouse TNFR2 is shown in the panels on the left. Mutated hTNFR2 constructs (m1, m2, m3, and m4) were used to narrow the binding site for different anti-hTNFR2 antibodies. Flow cytometry analysis revealed that mutations at amino acids 119–132 do not affect antibody binding, but mutations at amino acids 151–160 completely abolish binding of all antibodies. Mutations at amino acids 134–144 alter the binding of blocking and antagonist antibodies only, but do not significantly affect agonist antibodies. Dark gray bars indicate positive control, and white indicates negative control antibody. The dashed line represents the negative control antibody level. EXAMPLES The following section will describe specific, non-limiting examples that incorporate certain aspects of the invention. In many of the examples, particularly the in vivo examples, the 5-A05 antibody was used. This is a mouse antibody, which is a surrogate antibody for the human antibodies disclosed herein. It was selected as a surrogate antibody based on its characteristics similar to a non-ligand-blocking agonist antibody with a good EC50 value. In some of the examples and figures, a slightly different naming convention is used for the antibody clones, e.g., clone 001-F02 is sometimes abbreviated as 1-F02 or 1F02, 005-B08 is sometimes abbreviated as 5-B08 or 5B08, etc. Example 1: generation of specific antibodies against TNFR2 (See also Figure 1A to 1E and the previous description of this figure). Isolation of scFv antibody fragments The scFv n-Coder® collection (Biolnvent, Sóderlind E, et al. Nat Biotechnoi. 2000; 18(8):852-6) was used to isolate scFv antibody fragments that recognize human or mouse TNFR2. The phage pool was used in three consecutive screenings against recombinant human mouse protein (Sino Biological). After phage incubation, the cells were washed to remove unfixed phages. Fixing phages were eluted with trypsin and amplified in E. coii. The resulting phage pool was converted to scFv format. E. coii was transformed with LCLcnn / Lznz / B / Yi plasmids carrying scFv were used and individual scFv clones were expressed. Identification of unique TNFR2 fixation scFv The converted scFvs from the third screening were evaluated using a homogeneous FMAT assay (Applied Biosystems, Carlsbad, CA, USA) to determine attachment to 293 FT transfected cells expressing human or mouse TNFR2 or an unrelated protein. Briefly, transfected cells were added to clear-bottom plates, along with scFv-containing supernatant from expression plates (diluted 1:7), mouse anti-His tag antibody (0.4 pg / mL; R&D Systems), and an APC-conjugated goat anti-mouse antibody (0.2 pg / mL; C.N. 115-136-146, Jackson Immunoresearch). FMAT plates were incubated at room temperature for 9 h before reading. Bacterial clones that attached to cells transfected with TNFR2, but not to cells transfected with an unrelated protein, were classified as active and collected in a 96-well plate. IgG binding to TNFR2 in ELISA Ninety-six-well plates (Lumitrac 600 LIA plate, Greiner) were coated overnight at 4°C with recombinant mouse or human TNFR2-FC protein (Sino Biological) at 1 pmol / well. After washing, titrated doses of anti-TNFR2 mAb from 20 pg / mL to 0.1 ng / mL (133 nM to 1 pM) were allowed to bind for 1 hour. The plates were then washed again, and the bound antibodies were detected using a human anti-F(ab)-HRP secondary antibody (Jackson ImmunoResearch) diluted to 50 ng / mL. The Super Signal ELISA Pico (Thermo Scientific) was used as the substrate, and the plates were analyzed using a Tecan Ultra microplate reader. The data, shown in Table 5 and Figure 1A to ID, show that all anti-human TNFR2 antibodies bind to the human TNFR2 protein. EC50 values ​​range from 0.082 nM for 1-C08 to 4.4 nM for 1-A09. In addition, the mouse surrogate antibody clones 3-F10 and 5-A05 also bind to the mTNFR2 protein. These two clones bind with very similar affinity (Table 5 and Figure 1E). LCLcnn / Lznz / E / Yi Table 5. EC50 values ​​of antibodies that bind to the TNFR2 protein (human protein except for clones 3F10 v 5A05) LCLcnn / Lznz / B / Yi Clone ECso (nM) 1-C08 0.082 1-E06 0.20 1-G10 0.29 1-H10 0.29 4-H02 0.20 5-B02 0.15 5-B08 0.17 1-G04 1.7 1-H09 0.30 1-D01 0.37 5-F10 0.22 1-B11 0.25 1-C07 0.26 1-B05 0.23 1-F02 0.31 1-F06 0.15 4-E08 0.38 1-G05 0.54 1-A09 4.4 1-B09 0.18 1-C03 0.75 1-C05 0.38 3-F10 (mouse) 0.97 5-A05 (mouse) 1.4 Example 2: Antibody specificity (See also Figures 2A to 5B and the above description of these figures). Isolation of CD4+ T lymphocytes PBMCs were isolated from human bleukocyte layers and whole blood from Macaca fascicularis using Ficoll-Paque PLUS gradients (GE Healthcare). CD4+ T lymphocytes were isolated from the PBMCs by magnetic cell separation using the CD4+ T Lymphocyte Isolation Kit (Human) or non-human primate CD4 microspheres (Macaca fascicularis), both from Miltenyi. Mouse CD4+ T lymphocytes were isolated from the spleen using the CD4+ T Lymphocyte Isolation Kit (Mouse) from Miltenyi. n-CoDeR® antibody titration specific against TNFR2 The ability and affinity of n-CoDeR® antibodies against TNFR2 to bind to TNFR2-expressed cells were obtained using in vitro-activated CD4+ T lymphocytes. Human CD4+ T lymphocytes were stimulated with 50 ng / mL of rhIL-2 (R&D Systems) and Dynabeads® TActivator CD3 / CD28 for T cell expansion and activation (Gibco) for 2–3 days at 37°C. The in vitro-activated lymphocytes were labeled with increasing amounts of TNFR2-specific nCoDeR® antibodies or isotype control, ranging from 0.002–267 nM. The cells were then incubated with an APC-conjugated human IgG a secondary antibody (Jackson) followed by flow cytometry analysis (FACSVerse, BD). The resulting titration curves are shown in Figures 3A–3D. Mouse CD4+ T lymphocytes were stimulated with 135U / mL of rmIL-2 (R&D Systems) and Dynabeads® T-Activator CD3 / CD28 for T lymphocyte expansion and activation (Gibco) for 2-3 days at 37 degrees.In vitro activated lymphocytes were labeled with increasing amounts of TNFR2-specific n-CoDeR® antibodies or isotype control, ranging from 0.00003 to 133 nM. The cells were then incubated with an APC-conjugated mouse IgG a secondary antibody (Jackson) followed by flow cytometry analysis (FACSVerse, BD). Titration curves are shown in Figure 3E. EC50 values ​​for the titration curves were calculated using Microsoft Excel and are shown in Table 6. For the human antibodies, EC50 values ​​ranged from 0.6 nM (4-H02) to 52.7 nM (1-C03). Mouse antibodies were attached to activated lymphocytes in vitro with similar affinity (0.072 nM (3-F10) and 0.11 nM (5-A05)). Specificity of n-CoDeR® antibodies against TNFR2 The specificity of antibodies against TNFR2 was obtained in FACS blockade experiments with a commercial polyclonal TNFR2 antibody (R&D Systems). CD4+ T lymphocytes (mouse and human) stimulated for 2–3 days with 50 ng / mL rhIL-2 (R&D Systems) (human) / 135 U / mL rmIL-2 (R&D Systems) (mouse) and Dynabeads® T-Activator CD3 / CD28 for T lymphocyte expansion and activation (Gibco) were blocked with 40 pg / mL polyclonal TNFR2 antibody (R&D Systems) for 30 min, immediately followed by 15 min of incubation with n-CoDeR® antibodies against TNFR2 or isotype control. The concentration of nCoDeR® antibodies used was based on the titration curves for the individual nCoDeR® antibodies against TNFR2, and a suboptimal concentration was chosen for each antibody. Lymphocytes were then washed and incubated for 30 min with an APC-conjugated secondary antibody (Jackson).Lymphocytes were analyzed by flow cytometry (FACSVerse, BD). All binding of TNFR2-specific n-CoDeR® antibodies (both human and mouse) could be blocked by a polyclonal anti-TNFR2 antibody, as shown in Figure 4. These results verify that TNFR2-specific n-CoDeR® antibodies bind specifically to TNFR2 on CD4+ T lymphocytes activated in vitro. LCLcnn / Lznz / E / Yi Epitope mapping of n-CoDeR® antibodies specific against TNFR2 against the MR2-1 clone of the TNFR2 antibody The MR2-1 clone of antibody against TNFR2 (Invitrogen) binds to a specific domain of the TNFR2 protein. Whether n-CoDeR® antibodies specific against TNFR2 bound to the same domain as MR2-1 was evaluated using FACS blocking experiments. Human CD4+ T lymphocytes were stimulated for 2–3 days with 50 ng / mL of rhIL-2 (R&D Systems) and Dynabeads® T-Activator CD3 / CD28 for T lymphocyte expansion and activation (Gibco). Activated lymphocytes were blocked with 40 pg / mL of MR2-1 (black bars in Figure 5A), n-CoDeR® antibody specific against polyclonal TNFR2 / TNFR2 (R&D Systems) (black bars in Figure 5B), or PBS (gray bars in Figure 5A). After 30 min of incubation, lymphocytes were immediately stained for n-CoDeR® antibody specific against TNFR2 / pTNFR2 (Figure 5A) or MR2-1 (Figure 5B) for 15 min. The lymphocytes in Figure 5A were also incubated with an APC-conjugated secondary human IgG a reagent (Jackson). All lymphocytes were analyzed by flow cytometry (FACSVerse, BD).Since the percentage of MR21+ lymphocytes was the same for lymphocytes blocked by n-CoDeR® as for those not blocked (Figure 5B), and the binding of n-CoDeR® antibodies was the same with or without MR2-1 blockade (Figure 5A), these n-CoDeR® antibodies probably bind to other epitopes of the deTNFR2 protein in addition to the MR2-1 antibody. Fixation of n-CoDeR® antibodies against TNFR2 to Macaca fascicuaris To validate the cross-reactivity of antibodies against TNFR2 to Macaca fascicuaris, CD4+ T lymphocytes from Macaca fascicuaris were stimulated for 2 days with 50 ng / mL of PMA (Sigma) and 100 ng / mL of ionomyosin (Sigma). The lymphocytes were incubated with nCoDeR® antibodies specific to TNFR2 at 3 different concentrations (0.1, 1, and 10 pg / mL) and then incubated with a secondary human IgG a reagent conjugated to APC (Jackson). The cells were analyzed by flow cytometry (FACSVerse, BD), and the results show that most of the nCoDeR® antibodies specific to human TNFR2 could bind to Macaca fascicuaris TNFR2. The results for individual antibodies are presented in Figure 4. In summary, the data from Example 2 show that human antibodies specifically bind to endogenously expressed TNFR2 on human immune cells. Furthermore, the data show that this binding can be blocked by adding a commercially available polyclonal antibody against TNFR2, indicating very high specificity for TNFR2. The same holds true for the surrogate clones 3F10 and 5A05 with respect to murine cells expressing murine TNFR2. Moreover, the binding of the human clones is unaffected by the MR2-1 antibodies, which exhibit a different epitope specificity compared to MR2-1. LCLcnn / Lznz / E / Yi Table 6. ECso values ​​calculated on the titration of specific antibodies against TNFR2 against activated CD4+ T lymphocytes in vitro. LCLcnn / Lznz / B / Yi ECso clone (nM) 1-C08 2.6 1-E06 4.1 1-G10 3.3 1-H10 1.1 4-H02 0.59 5-B02 0.80 5-B08 1.2 1-G04 18 1-H09 16 1-D01 3.9 5-F10 32 1-B11 27 1-C07 36 1-B05 1.5 1-F02 0.79 1-F06 2.5 4-E08 2.3 1-G05 0.66 1-A09 48 1-B09 29 1-C03 53 1-C05 12 3-F10 (mouse) 0.072 5-A05 (mouse) 0.11 Example 3: Testing ligand blocking characteristics (See also Figures 6A to 7E and the description of these figures above). ELISA method 96-well plates were coated with hTNFRII (Sino Biological catalog no. nrl0414-H08H) or mTNFRII (Sino Biological catalog no. 50128 M08H) at 2.5 pmol / well in ELISA coating buffer (0.1 M sodium carbonate, pH 9.5) and incubated overnight at 4°C. After washing in ELISA wash buffer (PBS with 0.05% Tween20), the plates were incubated with slow shaking for 1 h at room temperature with mAb n-CoDeR® at 10 pg / mL (one-dose ELISA) or 33 nM and 1:2 subsequent dilutions (titration ELISA) in blocking buffer containing 0.45% fish gelatin. Subsequently, recombinant hTNF-α-bio (R&D catalog No. BT210) or mTNF-α (Gibco catalog No. PMC3014) was added to a final concentration of 5 nM and 2 nM, respectively, and the plates were incubated for a further 15 min. The plates were then washed. For the human ELISAs, streptavidin HRP (Jackson catalog No. BT210) was added.The substrate (Thermo Scientific Super Signal ELISA Pico, catalog No. 37069) was diluted 1:2000 in blocking buffer and incubated again for 1 h at room temperature, followed by washes first in ELISA buffer and then in Tris buffer (pH 9.8). The substrate (Thermo Scientific Super Signal ELISA Pico, catalog No. 37069) was then diluted according to the manufacturer's instructions, added to the cavities, and incubated in the dark for 10 min before reading on a Tecan Ultra. For the mouse ELISAs, rabbit anti-mTNF-α (Sino Biological catalog No. 50349-RP02) diluted to 1 pg / mL was added and incubated for 1 h at room temperature. After washing, rabbit anti-HRP diluted 1:10,000 in blocking buffer was added and incubated again for 1 h at room temperature. The addition and reading of the substrate were performed as described above. Data on anti-human and anti-mouse antibodies are presented in Tables 7 and 8, respectively, below, and in Figures 6A to 6E and 7A to 7E. Table 7. EC50 values ​​of human liqand-blocking antibodies: antibodies were titrated and EC50 values ​​were calculated. LCLcnn / Lznz / B / Yi EC50 Clone (nM) Block 001-H10 0.9 Complete 004-H02 0.4 Complete 005-B08 0.3 Complete 005-B02 0.2 Complete 001-E06 0.3 Partial 001-G10 1.6 Partial 001-C08 1.1 Partial 001-H09 1.4 Partial 005-F10 0.03 Partial 001-G04 3.2 Partial 001-B11 1.0 Weak 001-C07 0.8 Weak 001-D01 1.4 Weak Table 8. EC50 values ​​of murine liq-blocking antibodies: antibodies were titrated and EC50 values ​​were calculated. LCLcnn / Lznz / B / Yi EC50 Clone (nM) 3-F10 Block 1.9 Complete 4-C01 2.7 Complete 4-A06 2.0 Partial 4-A07 >500 Partial 4-F06 6.2 Partial 5-C09 8.6 Partial 2-D09 4.4 Partial 4-B12 >500 Partial 3-G06 13 Partial 2-H01 25 Weak 4-C02 >500 Weak 4-G09 2.6 Weak 4-C03 8.3 Weak Definitions of blockers • Complete blockers are defined as reducing TNF-α binding by more than 98%. • Partial blockers are defined as reducing TNF-α binding by 60-98%. • Weak blockers are defined as reducing TNF-α binding by less than 60%. • Non-blocking antibodies are defined as those that do not achieve more than 50% block in high-dose point ELISA, as shown in Figures 6A and 7A. The data shown in this example demonstrate that a variety of antibodies have been generated, ranging from those that completely inhibit TNF-α ligand binding to those that do not inhibit ligand blockade at all. This occurs for both human antibodies and murine surrogates. Example 4: In vitro functionality, antibodies (See also Figures 8A to 10D and the above description of these figures). Antibodies against TNFR2 that do not block TNF-q enhance IFN-γ production by cytokine-stimulated NK cells, unlike antibodies against TNFR2 that block TNF-q. The agonist / antagonist characteristics of specific antibodies against TNFR2 were evaluated using an NK cell assay described by Almishri et al. (TNFa Augments Cytokine-Induced NK Cell IFNy Production through TNFR2. Almishri W. et al. J Innate Immun. 2016;8:617-629). In summary, human NK cells were isolated from human PBMCs by MACS using an NK cell isolation kit (Miltenyi). 100 pL of NK cells (1 x 106 cells / mL) were cultured with 20 ng / mL of rhIL-2 (R&D Systems) and 20 ng / mL of rhIL-12 (R&D Systems) along with 10 pg / mL of TNFR2-specific antibodies, 10 pg / mL of isotype control, or 100 ng / mL of TNF-α (R&D Systems) in U-shaped bottom plates (96-cavity TC-treated Corning® microplates, Sigma-Aldrich). Supernatants were collected after 24 hours, and the amount of IFN-γ produced was assessed by MSD. As a control, the TNF-α neutralizing anti-TNF-α antibody (catalog no. AF-210-NA, R&D Systems) was included. As shown in Figure 8D, a dose of 1 pg / mL completely neutralized soluble TNF-α, and this dose also reduced IFN-γ release. Non-blocking human TNFR2 antibodies clearly enhanced IFN-γ production from IL-2 and IL-12 stimulated NK cells (2-3 times more IFN-γ than the isotype control), while antagonistic antibodies (shown here using complete blockers) showed antagonistic effects on IFN-γ production from NK cells (Figure 8A). This test was deemed unrepresentative for use with mouse surrogate antibodies due to the lack of endogenously produced TNF-α in murine cultures and the expression of inhibitory FcyR in murine NK cells and only activating FcyR in the human counterpart. Instead, the memory T cell activation assay (CD25 induction) and the myeloid-derived suppressor cell (MDSC) suppression assay (both described below) were used to assess the agonist or antagonist properties of the murine surrogate antibodies. Non-ligand-blocking antibodies against TNFR2 induce CD25 expression on memory CD4+ T lymphocytes To better understand the agonist / antagonist characteristics of antibodies against TNFR2, their ability to improve the proportion of CD4+ memory T lymphocytes expressing CD25 was evaluated. Briefly, human CD4+ T lymphocytes were isolated from PBMCs by MACS using the Miltenyi CD4+ T lymphocyte isolation kit. CD4+ T lymphocytes were cultured with 10 ng / mL of rhIL-2 (R&D Systems) and 10 pg / mL of TNFR2-specific antibody or the indicated amount of rhTNF-α (R&D Systems). After 3 days, CD25 expression was analyzed in LCLcnn / Lznz / B / Yi memory lymphocytes (CD45RO+ lymphocytes) by FACS (Figure 9A). Similarly, mouse CD4+ T lymphocytes were isolated from the spleen by MACS using the CD4+ T Lymphocyte Isolation Kit (Miltenyi) and cultured with 10 ng / mL of rmIL-2 (R&D Systems) and 10 pg / mL of TNFR2-specific antibody or the indicated amount of rmTNF-α (R&D Systems). CD25 expression in memory lymphocytes (CD44+CD62L' lymphocytes) was analyzed by FACS after 3 days (Figure 9B). The percentage of lymphocytes expressing CD25 increased in memory lymphocyte cultures stimulated with non-blocking TNFR2, again demonstrating agonist activity in both humans and mice. However, stimulation with blocking antibodies did not increase CD25 expression in these cultures. The ligand-non-blocking anti-TNFR2 mAb reverses the suppressor function of myeloid-derived suppressor cells (MDSCs) in T-cell / MDSC co-culture assays The impact of human anti-TNFR2 mAb on the suppressive function of MDSCs was evaluated in T-cell / MDSC co-culture assays. Briefly, MDSCs were generated by culturing human CD14+ monocytes isolated on MACS in 50% ascitic fluid isolated from cancer patients and 50% R-10 for 3 days. The MDSCs were then washed and pre-incubated with 10 pg / mL anti-TNFR2 mAb for 30 min. Without washing, the titers of MDSCs were co-cultured with CFSE-labeled CD3+ T cells isolated on MACS in the presence of CD3 / CD28 Dynabeads®. After 72 hours, the percentage of activated CD25+ T cells was assessed by FACS. IFN-γ and IL-10 secretion was measured using MSD according to the manufacturers' instructions. Unlike the blocking anti-TNFR2 mAb (dark gray bars), the non-blocking anti-TNFR2 mAb (light gray bars) was shown to increase the percentage of activated CD25+ in co-culture (Figure 10A). By measuring the amount of interferon-gamma (IFN-γ) and interleukin-10 secreted in the supernatant, the ratio of these two cytokines was used to estimate the Thl / Th2 balance. As shown in Figure 10B, the non-blocking anti-TNFR2 antibodies significantly increased the IFN-γ to IL-10 ratio compared to the blocking antagonist antibodies, indicating that the non-blocking antibodies induce a shift toward the Thl pathway. Regarding human antibodies, the effect of mouse anti-TNFR2 antibodies was evaluated using a similar suppression assay. CD11b+ myeloid cells were isolated directly on MACS from CT26 mouse tumors and pre-incubated for 30 min with anti-TNFR2 mAb. Responding CD3+ T lymphocytes were purified from untreated Balb / C spleens Previous LCLcnn / Lznz / B / Yi. Myeloid suppressor cells and CFSE-labeled T lymphocytes were co-cultured in different ratios for 3 days. The percentage of proliferating CFSE-low T lymphocytes was determined by FACS. Similar to the results of human assays, the percentage of proliferating responding lymphocytes is significantly lower after incubation with blocking antibodies than with non-blocking antibodies (Figure 10C). In MDCS suppression cultures, myeloid cells express high levels of various FcyRs. To assess whether the observed agonist and antagonist effects are Fe-dependent, the non-blocking 1F02 ligand agonist antibody was evaluated in several formats: hlgG1, which binds well to activating FcyRs; hIgG2, which also binds well to the inhibitor FcyRIIB; and an Fe-deficient format with severely reduced binding to all FcyRs. The results in Figure 10D show that the agonist activity of the non-blocking 1-F02 antibody is independent of antibody isotype and FcyR binding. In summary, the data from Example 4 show that non-ligand-blocking antibodies are agonists, as measured by several in vitro methods: NK cell-mediated IFN-γ release, CD4+ memory lymphocyte activation as measured by CD25 expression, and T lymphocyte proliferation and CD25 expression in an MDCS co-culture assay. Furthermore, the data show that this is an intrinsic characteristic independent of ligand presence and antibody isotype. The murine surrogate antibody 5A05 was also shown to have similar agonist characteristics. T-cell or NK cell-stimulating antibodies could be used in cancer treatment and could induce an endogenous immune response that ultimately inactivates malignant cells. Non-blocking antibodies against agonist ligands are shown according to the invention, while blocking antibodies against antagonist ligands are included for comparative purposes. Example 5: The mouse anti-TNFR2 mAb, a non-blocking surrogate ligand agonist, has an antitumor effect in vivo (See also Figures 11A to 17B and the above description of these figures). Therapeutic effect in different tumor models To evaluate the in vivo antitumor effect of non-ligand-blocking anti-TNFR2 agonist mAbs, a mouse surrogate, named 5-A05, was investigated in vivo in different tumor models, using different isotype formats, and alone or in combination with anti-PD-1 as described below. The mice were bred and kept in local facilities in accordance with the LCLcnn / Lznz / B / Yi local office guidelines. Taconic (Bomholt, Denmark) supplied six- to eight-week-old female BalbC and C57 / BL6 mice and housed them in local animal facilities. CT26, MC38, and B16 (ATCC) cells were cultured in glutamax-buffered RPMI supplemented with 10% FCS. When the cells were semiconfluent, they were separated with trypsin and resuspended in sterile PBS at 10 × 10⁶ cells / mL. Mice were injected subcutaneously with 100 µL of the corresponding cell suspension at 1 × 10⁶ cells / mouse. Three to eight days post-injection, depending on the model, mice were treated twice weekly with 10 mg / kg of ip antibody (isotype control, 3F10, or 5-A05) as shown in the figures. The tumors were measured twice a week until they reached a diameter of 15 mm, after which the mice were euthanized. The mouse anti-TNFR2 mAb, a non-blocking agonist of the 5-A05 ligand, shows an antitumor therapeutic effect in three different tumor models (Figure HA to 14C), with a curative effect in the more treatment-responding CT26 (Figure HA to 11B) and an inhibitory effect on tumor growth in the more treatment-resistant MC38 and B16 (Figures 12A to 12E to 14A to 14C). The antitumor effect of the non-ligand-blocking mouse anti-TNFR2 mAb does not require FcyR binding, but is potentiated by such binding. To assess the importance of the Fc-FcyR interaction in the in vivo antitumor effect of the mouse non-blocking 5A05 ligand agonist anti-TNFR2 mAb, different Fe formats of this antibody were investigated in vivo in the CT26 tumor model as described below. Mice were bred and maintained as described above. CT26 cells (ATCC) were cultured and injected as described above. When tumors reached 3 x 3 mm, mice were treated twice weekly with 10 mg / kg of ip antibody (isotype control, 5A05 IgG1, 5A05 IgG2a, or 5-A05-N297A (Fe-deficient)). Tumors were measured twice weekly until they reached a diameter of 15 mm, after which the mice were euthanized. The Fe-deficient 5-A05-N297A exhibits clear therapeutic activity compared to the isotype control, indicating that the interaction with Fe is not entirely responsible for the therapeutic efficacy of this non-ligand-blocking mouse anti-TNFR2 mAb (Figures 11A and 11B). Furthermore, both the IgG1 and IgG2a formats show enhanced therapeutic efficacy. However, the IgG1 format, which preferentially binds to inhibitory Fcy receptors, exhibits a superior therapeutic effect, suggesting that agonism is a key mechanism of action for this mouse anti-TNFR2 mAb (Figures 11A to 11B). This contrasts with the ligand-blocking antagonist surrogate antibody 3-F10, which shows no activity in the Fe-deficient format and exhibits the best activity in the murine IgG2a format, known for LCLcnn / Lznz / B / Yi preferably attach to the activating FcyR. The non-ligand blocking agonist antibody (5-A05) is according to the invention and the ligand blocking antagonist antibody (3-F10) is included by reference. Combined effect with anti-PD-1 mAb To evaluate the combined in vivo antitumor effect of anti-TNFR2 non-ligament-blocking mAb agonists, a mouse surrogate (5-A05) with anti-PD-1, the treatment combination was investigated in vivo in the MC38 tumor model as described below. Mice were bred and maintained as described above. MC38 cells (ATCC) were cultured and injected as described above. Eight days post-injection, mice were treated twice weekly with 10 mg / kg of ip antibody (isotype control, mouse anti-PD-1, 5-A05, or a combination of mouse anti-PD-1 and 5-A05) as shown in Figure 12A to 12E. Tumors were measured twice weekly until they reached a diameter of 15 mm, after which the mice were euthanized. Mouse anti-PD-1 and mouse anti-TNFR2 mAb, non-blocking agonists of the 5-A05 ligand, show a therapeutic effect on tumor growth inhibition in the MC38 model (Figures 12A to 12E). When anti-PD-1 and 5-A05 are combined, tumors are cured in treatment-resistant MC38 (Figures 12D to 12E). Combined effect with anti-PD-LL mAb To evaluate the combined antitumor effect of anti-TNFR2 agonist mAbs in iz / Vode, the mouse surrogate (5A05) was further combined with anti-PD-Ll for treatment in the MC38 tumor model as described below. Mice were bred and maintained as described above. MC38 cells (obtained from Dr. M. Cragg, University of Southampton) were cultured and injected as described above. Six days post-injection, mice were treated twice with isotype control antibody or 3F10 (days 1 and 4), or for four consecutive days with anti-PD-11 (clone 10F.9G2, Bioxcell) followed by a fifth injection two days later (five injections in total on days 1, 2, 3, 4, and 7), or a combination of both. All antibodies were administered at 10 mg / kg ip. Tumors were measured with calipers twice weekly until they reached a volume of 2000 mm³, after which the mice were euthanized. Mouse anti-PD-Ll and mouse anti-TNFR2 mAb 5A05 agonist show a therapeutic effect on tumor growth inhibition in the MC38 model (Figure 13). When anti-PD-Ll and mouse anti-TNFR2 mAb 5A05 antagonist are combined, the antitumor effect is further enhanced (Figure 13). LCLcnn / Lznz / E / Yi Modulation of immune cells in vivo To investigate the effects on immune cells in the tumor in vivo, BalbC mice were inoculated with CT26 cells as previously described. Once the tumors reached approximately 7 x 7 mm, the mice were treated with 10 mg / kg of antibodies administered intraperitoneally (ip) as shown in Figure 15A. Mice were treated on days 1, 4, and 7 and euthanized on day 8. The tumors were dissected, mechanically divided into small pieces, and digested using a mixture of collagenase (100 pg / mL liberase) and DNase (100 pg / mL) at 37°C for 2 x 5 min with vortexing between applications. After filtration through a 70 µm filter, the cell suspension was washed (400 g for 10 min) with PBS containing 10% FBS. The cells were then resuspended in MACS buffer and stained with either an antibody panel that stained CD45, CD3, CD8, CD4, and CD25 or an antibody panel that stained MHCII, F4 / 80, Ly6C, CDllb, and Ly6G.Prior to staining, cells were blocked for nonspecific fixation using 100 µg / mL of IVIG (purified intravenous immunoglobulin). Cells were analyzed using a FACS Verse. Mouse Tregs were quantified as CD45+CD3+CD4+CD25+ and TAM as CD11b+Ly6G-Ly6C'F4 / 80+MHCII+. As shown in Figures 15A–15D, treatment with the TNFR2 agonist antibody results in increased CD8+ T cell influx into the tumor. A weaker trend toward decreased Tregs is also observed. Together, these factors result in a significantly improved CD8+ to Treg ratio (Figure 15C). Furthermore, the agonist antibody modulates the myeloid compartment by reducing the number of tumor-associated macrophages. PBMC-NOG / SCID Model To confirm the in vitro findings of T lymphocyte proliferative activity of the anti-TNFR2 non-blocking 1-F02 ligand agonist mAb, the ability of this mAb to induce T lymphocyte proliferation in the PBMC-NOG model in vivo was analyzed as described below. Mice were bred and maintained in local facilities according to local office guidelines. Taconic (Bomholt, Denmark) supplied eight-week-old female NOG mice, which were maintained in local animal facilities. For the PBMCNOG (primary human xenograft) model, human PBMCs were isolated using Ficoll Paque PLUS and, after washing, the cells were resuspended in sterile PBS at 75 x 10⁶ cells / mL. NOG mice were injected intravenously with 200 pL of the cell suspension corresponding to 15 x 10⁶ cells / mouse. Two weeks post-injection, mice were treated twice (two days apart) with 10 mg / kg of isotype control, Yervoy, anti-CD25, Campath, 1-FO2, or 1-H10 (mAb). LCLcnn / Lznz / E / Yi anti-TNFR2 antagonist ligand blocker). Spleens were collected from mice 2 days after the last injection. Human T lymphocyte subsets were identified and quantified by FACS using the following markers: CD45, CD3, CD4, CD8, CD25, CD127 (all from BD Biosciences). In a separate experiment, spleens from untreated human PBMCs were collected to determine TNFR2 expression in human T lymphocytes by FACS (Figure 16). These FACS data showed that TNFR2 expression in TTreg and CD8+ T lymphocytes is highly comparable between cultured and activated human T lymphocytes in NOG mice and human tumor T lymphocytes. The 1-F02 induced T lymphocyte proliferation in accordance with what has been observed in vitro and in vivo with the mouse anti-TNFR2 surrogate agonist non-blocking ligand agonist mAb, whereas the 1-H10 antagonist did not induce proliferation (Figure 17A to 17B). In summary, Example 5 shows that: 1. Non-ligament-blocking agonist antibodies can have marked antitumor effects in several tumor models 2. This effect can be increased by combining it with anti-PD1 antibodies 3. Non-ligament-blocking agonist antibodies do not show an obligate dependence on FcyR for the antitumor effect, but the effect is enhanced by interaction with FcyR, mainly inhibitors. 4. Non-ligament-blocking agonist antibodies increase the influx of CD8+ T lymphocytes and decrease the number of Tregs in tumors. Furthermore, they decrease the number of TAMs in tumors, thus altering the composition of T lymphocytes and myeloid cells within the tumor. 5. In human tumors, T lymphocytes express TNFR2 6. In a human xenograft model in which tumor TNFR2 expression is mimicked in T lymphocytes, the non-blocking 1-F02 ligand agonist antibody increases the number of T lymphocytes. Example 6: Non-ligament-blocking agonist antibodies do not induce large amounts of pro-inflammatory cytokines (See also Figures 18A to 19C and the above description of these figures). The release of large amounts of proinflammatory cytokines is a possible side effect of immunomodulatory antibodies used to treat patients. Therefore, cytokine release induced by non-ligand-blocking agonist antibodies was measured using two different methods. The first is based on antibody stimulation. The first method uses LCLcnn / Lznz / B / Yi in vitro cultures, and the second is based on the xenograft of human immune cells in immunodeficient mice. For in vitro cultures, the preparation of the culture medium has been shown to greatly impact cytokine release (Vessillier et al., J Immunol Methods. September 2015; 424: 43-52). To account for differences in methodologies, three different in vitro culture setups were used, in accordance with recent publications. For cytokine release assays (CRA) in high-density cell culture (HDC), PBMCs were cultured at 1 x 10⁷ cells / mL in serum-free CTL-Test medium (Cell Technology Limited) supplemented with 2 mM glutamine, 1 mM pyruvate, 100 µU / mL penicillin, and streptomycin. Two milliliters of cell culture were placed in a 12-well plate. After 48 h, 10 µg / mL of antibody was added to pre-incubated 1 x 10⁵ PBMCs in a 96-well flat-bottom plate, and the plate was incubated for 24 h. Solid-phase CRA (SP) of PBMC was performed by coating the cavities of a 96-cavity plate with 1 pg / mL of antibody for 1 h. After washing the plate with PBS, 1x105PBMC were added to 200 pL of complete medium per cavity and incubated for 48 h. Cytokine release was also measured after stimulation of 200 pL of whole blood with 5 pg / mL antibody for 48 h. At the end of the incubation period, the plates were centrifuged, and the culture supernatant was collected and stored at -20°C. The concentrations of IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-8, and TNF-α were measured using custom MSD plates, according to the manufacturer's instructions (Meso Scale Discovery, USA). In summary, non-ligament-blocking agonist antibodies induced significant cytokine release beyond IFN-γ in any of the in vitro environments (data not shown). The positive control antibodies, alemtuzumab and OKT3, induced cytokines, the most pronounced of which was IFN-γ. As shown in Figures 18A to 18C, the non-ligament-blocking agonist antibodies did not induce IFN-γ in two of the three in vitro environments; furthermore, antibody 1-F02 did not induce IFN-γ in any of the in vitro environments. PBMC-NOG Tolerability Model To investigate the tolerability of the non-blocking 1-F02 ligand-anti-TNFR2 mAb, cytokine release was analyzed in vivo in the PBMC-NOG model as described below. Mice were bred and maintained in local facilities according to local office guidelines. Taconic (Bomholt, Denmark) supplied eight-week-old female NOG mice, which were maintained in local animal facilities. For the PBMCNOG (primary human xenograft) model, human PBMCs were isolated using Ficoll Paque LCLcnn / Lznz / B / Yi PLUS, and after washing, the cells were resuspended in sterile PBS at 125 x 10⁶ cells / mL. NOG mice were injected intravenously with 200 pL of the cell suspension corresponding to 25 x 10⁶ cells / mouse. Two weeks after injection, blood samples were taken to assess the level of humanization, i.e., the number of human cells in the blood of the NOG mice. When the blood was composed of approximately 40% human T lymphocytes, the mice were considered humanized. The mice were then treated with 10 pg of Yervoy, anti-CD3 (OKT-3), 1-FO2, or isotype control mAb. Body temperature was measured before antibody injection and 1 h after injection (Figure 19A). As seen in Figure 19A, the OKT3 positive control antibody induced a drastic decrease in body temperature as previously reported, and in accordance with the toxicity observed in the clinic with this antibody.In contrast, 1-F02 showed no effect on body temperature. Five hours after antibody injection, the experiments were terminated, and blood was collected for cytokine release (MSD) analysis. The cytokines measured were human IFN-γ, TNF-α, IL-6, and IIAβ. Of these, IFN-γ and TNF-α were quantified at sufficiently high levels to be reliable. As shown in Figures 19B and 19C, the positive control antibody OKT3 induced significant release of both IFN-γ and TNF-α (consistent with the toxicity observed clinically with this antibody), while mice treated with 1-F02 did not have significant IFN-γ release. However, there was a trend toward increased TNF-α release, although not significant and not as dramatic as for OKT3. In summary, Example 6 shows that non-ligand-blocking TNFR2 agonist antibodies, exemplified here by the antibody designated 1-F02, do not induce substantial levels of cytokine release as measured by several previously published methods. Since cytokine release is a limiting factor for several immunomodulatory antibodies, this indicates an acceptable safety profile in this respect. Example 7: eoitooos of antibodies directed against TNFR2 generated Domain construct inactivations In the first set of experiments, DNA constructs encoding different TNFR2 variants were used, each lacking one or more of the four extracellular domains described in Table 9. In the second set of experiments, DNA constructs encoding TNFR2 variants were used in which different parts of domain 3 were exchanged with the corresponding murine portion, as described in Table 10. This latter exchange is possible because none of the antibodies exhibit cross-reactivity with murine TNFR. In both cases, the constructs were acquired through GeneArt (ThermoFisher). LCLcnn / Lznz / B / Yi were cloned into an expression vector, which contained the CMV promoter and the origin of replication of the OriP plasmid, and were transiently expressed in suspension-adapted HEK293-EBNA cells. Table 9. TNFR2 constructs used for transfection in which one or more domains have been removed. LCLcnn / Lznz / B / Yi Construct Description hTNFR2 Full-length wild-type human TNFR2 (Uniprot #P20333) hTNFR2-Al hTNFR2 with TNFR-Cys domain 1 (aa 39-76) deleted hTNFR2-A2 hTNFR2 with TNFR-Cys domain 2 (aa 77-118) deleted hTNFR2-A3 hTNFR2 with domain TNFR-Cys 3 (aa 119-162) deleted hTNFR2-A4 hTNFR2 with TNFR-Cys domain 4 (aa 163-201) deleted hTNFR2-Al+3 hTNFR2 with TNFR-Cys domains 1 and 3 (aa 39-76 and 119-162) deleted hTNFR2-A2+4 hTNFR2 with TNFR-Cys 2 and 4 domains (aa 77-118 and 163-201) eliminated Table 10. Several parts of domain 3 of the TNFR2 constructs used for transfection have been exchanged for the corresponding murine sequence. Construct Description hTNFR2 Full-length wild-type human TNFR2 (Uniprot No. P20333) mTNFR2 Full-length wild-type murine TNFR2 (Uniprot No. P25119) hTNFR2-ml hTNFR2 with aa 119-132 replaced by aa 120-133 from mTNFR2 hTNFR2-m2 hTNFR2 with aa 134-144 replaced by aa 135-146 from mTNFR2 hTNFR2-m3 hTNFR2 with aa 151-160 replaced by aa 153-162 from mTNFR2 hTNFR2-m4 hTNFR2 with aa 130-144 replaced by aa 131-146 from mTNFR2 Flow cytometry-based fixation analysis HEK-293-E cells were transfected with the respective TNFR2 variant cDNA plasmids using Lipofectamine 2000. Forty-eight hours after transfection, the cells were harvested and stained with the indicated antibodies for 30 minutes. After two washes with PBS, the surface-bound antibodies were stained with an APC-coupled secondary anti-IgG. Prior to flow cytometry analysis on a BD-Verse flow cytometer, the cells were washed and stained with Live / Dead. Flow cytometry-based fixation experiments of transfected HEK 293 cells clearly showed that domain 1 and domain 2 do not affect fixation (domain 1), or only marginally affects the binding (domain 2) of any of the antibodies to these cells. A polyclonal anti-human TNFR2 antibody was used as a positive control. The positive control antibody showed high binding to all constructs evaluated, while the negative control antibody showed no binding (Figure 20A to 20F). All antibodies evaluated showed a complete loss of binding to TNFR2 lacking domain 3. Similarly, most antibodies failed to bind to TNFR2 if domain 4 was missing. All antagonistic antibodies (1H10, 4H02, and 5B08) showed drastically reduced binding to TNFR2 Δ4 by more than 50% compared to binding to TNFR2 Δ1 and TNFR2 Δ2.Similarly, the deletion of two domains of TNFR2 clearly showed that the absence of domain 3 or 4 severely abolished the binding of all evaluated antibodies to TNFR2, with the possible exception of the agonist antibody 1F06, while the absence of domain 4 eliminated the binding of agonist antibodies and significantly reduced the binding of antagonist antibodies. (Figure 20E and 20F). Chimeric mouse-human TNFR2 fixation To further reduce the binding site and define the epitopes, portions of domain 3 of human TNFR2 were replaced with the corresponding mouse sequence. Since all antibodies show very little cross-reactivity with mouse TNFR2, a loss of binding to certain constructs would allow for refinement of the binding epitope. Figure 21 shows the different chimeric mouse-human TNFR2 constructs. Four different replacements were performed, by exchanging 14 (m1), 12 (m2), 10 (m3), or 16 (m4) amino acids of the human sequence with the corresponding mouse sequence. The other three domains (1, 2, 4) contain exclusively human sequences. These constructs (TNFR2 domains 1-4 with mutations in 3) were then transfected into HEK293 cells, and antibody binding was assessed using a flow cytometry approach. Polyclonal antibodies against mouse TNFR2, as well as against human TNFR2, were used as positive controls. As expected, due to sequence similarity, both polyclonal control antibodies showed significant cross-reactivity and recognized both human and mouse TNFR2. The strongest signals were obviously obtained when the antibodies were paired with their intended target. The present monoclonal antibodies showed strong binding to human TNFR2, but little or no binding to mouse TNFR2 (Figure 22, panels on the left). Similar binding with very little reduction was observed for all clones to the hTNFR2 construct mi with mutations in aa 119–132, indicating that none of the antibodies bind to an epitope within that region. However, mutations in aa 134–144 (hTNFR2 construct) showed reduced binding. LCLcnn / Lznz / E / Yi m2) completely abolished binding in half of the evaluated antibodies, corresponding to the antagonistic blocking antibodies 1-H10, 4-H02, and 5-B08, indicating that the antibodies bind at least partially within this region. 1-G10, a partial blocker, is also strongly affected by this replacement. Notably, the agonist antibodies (1-F02, 1F06, and 4-E08) retained binding using construct 2, strongly suggesting a different epitope compared to the antagonist antibodies. Interestingly, all antibodies lost binding to the hTNFR2 m3 construct with mutations in aa 151-160. This indicates that all antibodies, both agonists and antagonists, have a partial epitope within that sequence. Testing a slightly larger hTNFR2 m4 construct with mutations in aa 130-144 showed fixation similar to that of the hTNFR2 m2 construct. Conclusions about fixation epitopes When grouping antibodies according to their function, the agonist antibodies (1-F02, 1-F06, and 4-E08) appear to bind to a very distal portion of the C-terminus of domain 3 spanning amino acids 151-160 and probably extend into a larger portion of domain 4, while the epitope for the antagonists (1-H10, 5-B08, and 4-H02) shifts more towards the center of domain 3, spanning amino acids 134-160, and probably covers a smaller portion of domain 4. However, despite this, their epitopes appear to overlap to some extent. None of the antibodies bind to the N-terminal portion of domain 3, aa 119134. Binding sites to domain 4 are fairly likely for all antibodies, but have not been fully identified.

Claims

1. - An agonist antibody molecule that binds specifically to TNFR2 on a target cell and wherein the antibody molecule does not block the binding of the TNF-α ligand to TNFR2.

2. An antibody molecule according to claim 1, wherein the antibody molecule has intrinsic agonist activity.

3. An antibody molecule according to claim 1 or 2, wherein the antibody molecule is also bound to an Fcy receptor.

4. An antibody molecule according to any of claim 13, wherein the antibody molecule binds with greater affinity to inhibitory Fcy receptors than to activating Fcy receptors.

5. An antibody molecule according to any of claim 14, wherein the binding of the antibody molecule to TNFR2 results in a change in the quantity and / or frequency of cells expressing TNFR2 in diseased tissue.

6. An antibody molecule according to any of claim 15, wherein the attachment of the antibody molecule to TNFR2 results in the infiltration of T lymphocytes and / or myeloid cells into the diseased tissue and / or a change in the composition of T lymphocytes and / or myeloid cells in the diseased tissue. 7 - An antibody molecule according to any of claim 16, wherein the antibody molecule is selected from the group consisting of: a full-size antibody, a chimeric antibody, a divalent or multivalent antibody molecule comprising single-stranded antibodies, Fab, Fvs, scFv, Fab's and / or (Fab')2 and an antigen-binding fragment thereof. 8.- An antibody molecule according to any of claim 17, which binds to human TNFR2 (hTNFR2) and / or Macaca fascicu / aris TNFR2 (cmTNFR2).

9. An antibody molecule according to any of claim 18, wherein the antibody molecule is selected from the group consisting of a human IgG antibody molecule, a humanized IgG antibody molecule, and a human-derived IgG antibody molecule.

10. An antibody molecule according to claim 9, wherein the antibody molecule is a human IgG2 antibody.

11. An antibody molecule according to any of claims 1-10, wherein the antibody molecule is a monoclonal antibody. LCLcnn / Lznz / E / Yi 12. An antibody molecule according to any of claims 1-11, wherein the antibody molecule is not specifically bound to an epitope comprising or consisting of the sequence KCSPG.

13. An antibody molecule according to any one of claims 1-12, wherein the antibody molecule is selected from the group consisting of antibody molecules comprising 1-6 of the CDRs VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2 and VL-CDR3, wherein VH-CDR1, if present, is selected from the group consisting of SEQ ID NO: 1, 9, 17, 25, 33, 41, 49, 57, 65, 73, 81, 89 and 97; wherein VH-CDR2, if present, is selected from the group consisting of SEQ ID NO: 2, 10, 18, 26, 34, 42, 50, 58, 66, 74, 82, 90 and 98; where VH-CDR3, if present, is selected from the group consisting of SEQ ID NO: 3, 11, 19, 27, 35, 43, 51, 59, 67, 75, 83, 91 and 99; where VL-CDR1, if present, is selected from the group consisting of SEQ ID NO: 4, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92 and 100; where VL-CDR2, if present, is selected from the group consisting of SEQ ID NO: 5, 13, 21, 29, 37, 45, 53, 61, 69, 77, 85, 93 and 101;and where VL-CDR3, if present, is selected from the group consisting of SEQ ID NO: 6, 14, 22, 30, 38, 46, 54, 62, 70, 78, 86, 94 and 102.; 14. An antibody molecule according to any of claims 1-13, wherein the antibody molecule comprises a variable heavy chain (VH) comprising the following CDRs: (I) SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; or (i) SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11; or (iii) SEQ ID NO: 17, SEQ ID NO: 18 and SEQ ID NO: 19; or (iv) SEQ ID NO: 25, SEQ ID NO: 26 and SEQ ID NO: 27; or (v) SEQ ID NO: 33, SEQ ID NO: 34 and SEQ ID NO: 35; or (vi) SEQ ID NO: 41, SEQ ID NO: 42 and SEQ ID NO: 43; and / or wherein the antibody molecule comprises a variable light chain (VL) comprising the following CDRs: (I) SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6; or (i) SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14; or (iii) SEQ ID NO: 20, SEQ ID NO: 21 and SEQ ID NO: 22; or (iv) SEQ ID NO: 28, SEQ ID NO: 29 and SEQ ID NO: 30; or (v) SEQ ID NO: 36, SEQ ID NO: 37 and SEQ ID NO: 38; or (vi) SEQ ID NO: 44, SEQ ID NO: 45 and SEQ ID NO:

46.

15. An antibody molecule according to any of claims 1-14, wherein the antibody molecule comprises a variable heavy chain (VH) amino acid sequence selected from the group consisting of SEQ ID NO: 7, 15, 23, 31, 39, 47, 55, 63, 71, 79, 87, 95 and 103; and / or wherein the antibody molecule comprises a variable light chain (VL) amino acid sequence selected from the group consisting of SEQ ID NO: 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 and 104.

16. An antibody molecule according to any of claims 1-15, wherein the antibody molecule comprises a variable heavy chain (VH) amino acid sequence selected from the group consisting of SEQ ID NO: 7, 15, 23, 31, 39 and 47, and LCLcnn / Lznz / E / Yi a variable light chain (VL) amino acid sequence selected from the group consisting of SEQ ID NO: 8, 16, 24, 32, 40 and 48.

17. An antibody molecule according to any of claims 112, wherein the antibody molecule is an antibody molecule that is capable of competing for binding to TNFR2 with an antibody molecule as defined in any of claims 13-16.

18. An isolated nucleotide sequence encoding an antibody molecule as defined in any of claims 1-17.

19. A plasmid comprising a nucleotide sequence as defined in claim 18.

20. A virus comprising a nucleotide sequence as defined in claim 18 or a plasmid as defined in claim 19.

21. A virus according to claim 20, further comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor. 22 - A cell comprising a nucleotide sequence as defined in claim 18, or a plasmid as defined in claim 19, or a virus as defined in claim 20 or 21.

23. An antibody molecule as defined in any of claims 1-17, a nucleotide sequence according to claim 18, a plasmid according to claim 19, a virus according to claim 20 or 21 and / or a cell according to claim 22 for use in medicine. 24 - An antibody molecule as defined in any of claims 1-17, a nucleotide sequence according to claim 18, a plasmid according to claim 19, a virus according to claim 20 or 21 and / or a cell according to claim 22 for use in the treatment of cancer or a chronic inflammatory disease in a patient.

25. The antibody molecule, nucleotide sequence, plasmid, virus and / or cell for use according to claim 24, wherein the patient to be treated is a patient who has a high expression of TNFR2 in diseased tissue.

26. An antibody molecule as defined in any of claims 1-17, a nucleotide sequence according to claim 18, a plasmid according to claim 19, a virus according to claim 20 and / or a cell according to claim 22, for use in the treatment of cancer in combination with: an antibody molecule that specifically binds to a checkpoint inhibitor; an LCLcnn / Lznz / B / Yi nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor; a plasmid comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor;and / or a cell comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, a plasmid comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, or a virus comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor.

27. The use of an antibody molecule as defined in any of claims 1-17, a nucleotide sequence according to claim 18, a plasmid according to claim 19, a virus according to claim 20 and / or a cell according to claim 22 for the preparation of a pharmaceutical composition for use in the treatment of cancer or a chronic inflammatory disease in a patient.

28. The use as claimed in claim 27, wherein the patient to be treated is a patient who has a high expression of TNFR2 in diseased tissue.

29. The use as claimed in claim 27 or 28, wherein the pharmaceutical composition is adapted to be administered in combination with: an antibody molecule specifically binding to a checkpoint inhibitor; a nucleotide sequence encoding an antibody molecule specifically binding to a checkpoint inhibitor; a plasmid comprising a nucleotide sequence encoding an antibody molecule specifically binding to a checkpoint inhibitor;and / or a cell comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, a plasmid comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, or a virus comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor.

30. A pharmaceutical composition comprising or consisting of an antibody molecule as defined in any of claims 1-17, a nucleotide sequence according to claim 18, a plasmid according to claim 19, a virus according to claim 20 and / or a cell according to claim 22 and, optionally, a pharmaceutically acceptable diluent, carrier, vehicle and / or excipient.

31. A pharmaceutical composition according to claim 30, for use in the treatment of cancer or a chronic inflammatory disease.

32. A pharmaceutical composition for use according to claim 31, for use in the treatment of cancer in combination with a pharmaceutical composition that LCLcnn / Lznz / E / Yi comprises: an antibody molecule specifically binding to a checkpoint inhibitor; a nucleotide sequence encoding an antibody molecule specifically binding to a checkpoint inhibitor; a plasmid comprising a nucleotide sequence encoding an antibody molecule specifically binding to a checkpoint inhibitor;and / or a cell comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, a plasmid comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor, or a virus comprising a nucleotide sequence encoding an antibody molecule that specifically binds to a checkpoint inhibitor.

33. The antibody molecule for use according to claim 26, the nucleotide sequence for use according to claim 26, the plasmid for use according to claim 26, the virus according to claim 21, the virus for use according to claim 26, the cell for use according to claim 26, the use as claimed in claim 29, or the pharmaceutical composition for use according to claim 32, wherein the checkpoint inhibitor is PD-1.

34. The antibody molecule for use according to claim 26, the nucleotide sequence for use according to claim 26, the plasmid for use according to claim 26, the virus according to claim 21, the virus for use according to claim 26, the cell for use according to claim 26, the use as claimed in claim 29, or the pharmaceutical composition for use according to claim 32, wherein the checkpoint inhibitor is PD-L1.

35. The antibody molecule for use according to claim 24, 25, 26, 33 or 34, the nucleotide sequence for use according to claim 24, 25, 26, 33 or 34, the plasmid for use according to claim 24, 25, 26, 33 or 34, the virus for use according to claim 24, 25, 26, 33 or 34, the cell for use according to claim 24, 25, 26, 33 or 34, the use according to claim 27, 28, 29, 33 or 34, or the pharmaceutical composition according to claim 31, 32, 33 or 34, wherein the cancer type is a solid cancer type.