Ltbr binding molecules and uses thereof

Abstract

Provided herein are anti-LTßR multispecific binding molecules, nucleic acids encoding the anti- LTßR multispecific binding molecules, vectors comprising the nucleic acids, host cells comprising the vectors, and pharmaceutical compositions comprising the anti-LTßR multispecific binding molecules. Also provided are methods of treating cancer in a subject in need thereof, the methods comprising administering the pharmaceutical compositions disclosed herein.

Description

093699.0207 PATENT LTΒR BINDING MOLECULES AND USES THEREOF CROSS-REFERENCES TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 634,038, filed April 15, 2024, the content of which is incorporated herein by reference in its entirety, and to which priority is claimed. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in xml format and is hereby incorporated by reference in its entirety. Said xml file, created on April 15, 2025, is named 0936990207.xml and is 2,358,903 bytes in size. FIELD OF THE INVENTION This invention relates to anti-LTΒR binding molecules, nucleic acids and expression vectors encoding the binding molecules, recombinant cells containing the vectors, and compositions comprising the binding molecules. This invention further relates to anti-LTΒR multispecific binding molecules, nucleic acids and expression vectors encoding the binding molecules, recombinant cells containing the vectors, and compositions comprising the binding molecules. Methods of making the binding molecules, and methods of using the binding molecules to kill cancer cells, are also provided. BACKGROUND OF THE INVENTION Immunotherapy of cancer has the potential to improve the survival of cancer patients by promoting an immune response towards the tumor. While certain patients experience deep and long responses to currently available anti-cancer immunotherapy (e.g. anti-CTLA4 antibody ipilimumab, anti-PD-1 / PD-L1 antibodies such as pembrolizumab or nivolumab), a large fraction of patients do not benefit from the such therapies (Ribas et al., Science 359:1350-1355 (2018)). For instance, patients that have so called “cold” or non-inflamed tumors that are characterized by the lack of immune cell infiltrate or by the absence of an inflammatory signature have a lower benefit from anti-cancer immunotherapies (Chen and Mellman, Nature 541:321-30 (2017)). Thus, there is a need for novel anti-cancer immunotherapies to improve the efficacy in non-inflamed tumors. Targeting lymphotoxin-β receptor (LTβR) shows promise as a modality of enhancing treatment approaches in the field of cancer immunotherapy (Skeate, J. G., et al., 2020, Front Immunol, 11:922). The receptors of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) are particularly of interest as targets for immunotherapy. The TNFRs are characterized by a cysteine-093699.0207 PATENT rich domain (CRD) which can be found in their ectodomain in one to six copies (Locksley et al, Cell, 104:487-501 (2001)). The CRDs are involved in ligand binding but can also promote receptor self-assembly. The TNFRs become activated by ligands of the TNF superfamily (TNFSF) (Locksley et al, Cell, 104:487-501 (2001); Bodmer et al, Trends Biochem Sci, 27:19-26 (2002)). The TNFSF ligands (TNFLs) form a structurally comparatively homogeneous protein family and are characterized by a C-terminal TNF homology domain (THD), which promotes the assembly into homotrimeric, and in a few cases also into heterotrimeric, molecules (Bodmer et al, Trends Biochem Sci, 27:19-26 (2002)). In the trimeric state, the THD mediates the interaction with the receptors of the TNFRSF. The signaling competent TNFRs differ in their response to soluble ligand trimers. The group called category I TNFRs are robustly activated by soluble ligand trimers, while the anchoring-dependent mode of receptor activation has been demonstrated for several category II TNFRs. The region between the last CRD domain and the transmembrane domain of the receptor plays an important role in the activation by soluble ligand trimers, with receptors having a shorter region, among which is LTβR, being more readily activated by soluble ligand (category I TNFRs). Thus, it has been perceived that TNFR-type intrinsic properties, and not the quality of the ligand, determine the responsiveness of TNFRs to TNFLs. LTβR is a single-pass receptor that, like other TNFR superfamily members, is thought to exist as a trimer expressed on the cell surface and can be activated by binding either of its TNFSF ligands: LTα1b2 or LIGHT, primarily through the two central CRDs, while the N-terminal CRD may mediate formation of a signaling-inactive pre-ligand assembly state. Additionally, distinct regions within the cytoplasmic domain mediate self-interaction and the transmembrane helix itself may also regulate signaling (Sautes-Fridman, C., et al., 2019, Nat Rev Cancer, 19:307-325; Schumacher, T. N. & Thommen, D. S., 2022, Science, 375:eabf9419). While the minimal signaling unit of TNF receptors is a trimer and several mechanistic studies support the hypothesis that the efficiency of TNF receptor signaling is related to the degree of hexamer or higher-order network formation in the cell membrane (Vanamee, E.S. and Faustman, D.L., 2023, Frontiers in Immunology, 14:1225704; Fromm et al., 2023, Frontiers in Immunology, 14:1236332), unlike other TNF receptors, each LTβR subunit can bind only two sites in the LTα1β2 heterotrimer, the LTα-LTβ (higher affinity) and the LTβ-LTβ′ (lower affinity) interfaces for productive receptor activation (Sudhamsu, J., et al., 2013, Proc Natl Acad Sci USA, 110:19896-19901). Similarly, LIGHT has been shown to present only two high-affinity binding sites for LTβR (Eldredge, J., et al., 2006, Biochemistry, 45:10117-10128). Thus, the binding of LTα1β2 or LIGHT to LTβR brings two receptor molecules in close proximity and the LTβR self-interaction region in the cytoplasmic093699.0207 PATENT domain promotes receptor aggregation and consequent conformational changes (Force, W. R., et al., 2000, J Biol Chem, 275:11121-11129). When LTβR is activated within tumors it induces tumor cell apoptosis directly, as well as significant changes in the tumor microenvironment that are primarily driven through vascular normalization and generation of tertiary lymphoid structures (Rooney, I. A., et al., 2000, J Biol Chem, 275:14307-14315). These changes can synergize with methods that induce or support anti- tumor immune responses, such as checkpoint inhibitors and / or tumor vaccines, to greatly improve immunotherapeutic strategies against cancer. Despite lacking a cell death domain in its cytosolic tail, LTβR has been shown to induce death of cancer cell lines and to arrest tumor growth in cell line-derived xenograft models (Browning, J. L., et al., 1996, J Exp Med, 183:867-878; Lukashev, M., et al., 2006, Cancer Res, 66:9617-9624). LTβR activation was shown to lead to cell death in the presence of IFN-γ by either caspase-dependent (apoptosis) and / or caspase-independent (necroptosis / necrosis) mechanisms (Browning, J. L., et al., 1996, J Exp Med, 183:867-878; Kuai, J., et al., 2003, J Biol Chem, 278:14363-14369; Chen, M. C., et al., 2000, J Biol Chem, 275:38794-38801; Chen, M. C., et al., 278:16073-16081; Hu, X., et al., 2013, Carcinogenesis, 34:1105-1114; Wilson, C. A & Browning, J. L., 2002, Cell Death Differ, 9:1321-1333). In fact, at least two independent signaling pathways are initiated by LTβR ligation, LTβR cell death signaling and NF-κB activation (VanArsdale, T. L., et al., 1997, Proc Natl Acad Sci USA, 94:2460-2465). Most TNFRs contain one or more short binding motifs for proteins of the TNF receptor- associated factor (TRAF) family which link these TRAF-interacting TNFRs to intracellular signaling pathways enabling the activation of transcription factors of the NF-κB family and various MAP kinase cascades (Xie, 2013; Park, 2018). NF-κB activation and cell death induction are the best characterized events downstream LTβR. Unlike the prototypical TNF receptors, which activate the classical but not the alternative NF-κB pathway, LTβR binding by its ligands leads to both classical and alternative NF-κB pathway activation (Ganeff, C., et al., 2011, Mol Cell Biol, 31:4319-4334; Dejardin, E., et al., 2002, Immunity, 17:525-535). Ligand binding to LTβR can induce a rapid and transient activation of the classical NF-κB pathway, followed by a delayed activation of the alternative pathway (Dejardin, E., et al., 2002, Immunity, 17:525-535; Scheu, S., et al., 2002, J Exp Med, 195:1613-1624). The activation of one or the other NF-κB signaling pathway is spatially and temporally regulated by LTβR trafficking and varying levels of receptor cross-linking may be required for distinct conformational changes and activation of different signal transduction pathways controlling distinct patterns of gene expression and therefore differentially093699.0207 PATENT involved in various functions attributed to LTβR signaling (Ganeff, C., et al., 2011, Mol Cell Biol, 31:4319-4334; Dejardin, E., et al., 2002, Immunity, 17:525-535). Through activation of the classical NF-κB pathway, LTβR signaling promotes the upregulation of pro-inflammatory molecules, including the CCL4 / macrophage inflammatory protein (MIP)-1β, CXCL2 / MIP-2, and vascular-cell adhesion molecule 1 (VCAM-1), and CXCL1, CXCL2, intercellular adhesion molecule 1 (ICAM-1), VCAM-1, and E-selectin (Dejardin, E., et al., 2002, Immunity, 17:525-535; Madge, L. A., et al., 2008, J Immunol, 180:3467-3477). Conversely, the LTβR-mediated activation of alternative NF-κB pathway results in the production of lymphoid chemokines such as the CCL19 / EBl1-ligand chemokine (ELC), CCL21 / secondary lymphoid tissue chemokine (SLC), CXCL12 / stromal cell-derived factor-1α (SDF-1α), CXCL13 / B lymphocyte chemoattractant (BLC), and the cytokine B cell activation factor (BAFF), being all involved in lymphoid organogenesis and homeostasis (Dejardin, E., et al., 2002, Immunity, 17:525- 535; Seach, N., et al., 2008, J Immunol, 180:5384-5392). The signal transduction results in formation of the HEV, recruitment of immune cells, and organization of the nascent tertiary lymphoid structures (TLS), organized cell aggregates resembling secondary lymphoid organs that form in non-lymphoid tissues, such as cancer, in response to chronic inflammatory states (Sautes- Fridman, C., et al., 2019, Nat Rev Cancer, 19:307-325; Asrir, A., et al., 2022, Cell, 40:318-334; Vanhersecke, L., et al., 2021, Nat Cancer, 2:794-802). The core immune cohort is comprised of CD20+B cells, CD3+T cells, CD21+follicular dendritic cells, CD138+plasma cells, dendritic cells, CD66+neutrophils, CD68+macrophages, and high endothelial venules (HEVs) (Petitprez, F., et al., 2020, Front Immunol, 11:784). The presence of tumor-associated TLS is associated with more favorable prognosis in cancer patients and response to immune checkpoint therapies (Asrir, A., et al., 2022, Cell, 40:318-334; Vanhersecke, L., et al., 2021, Nat Cancer, 2:794-802). Activation of LTβR has the potential to promote TLS formation in the tumor microenvironment and induce anti- tumor immune responses and improve current cancer immunotherapies. In particularly in immune- non-inflamed deserted solid tumor phenotypes characterized by the lack of immune cell infiltrate or by the absence of an inflammatory signature (e.g. bladder, uterine, adrenocortical, and prostate tumors) (Sautes-Fridman, C., et al., 2019, Nat Rev Cancer, 19:307-325; ). Indeed, in preclinical studies, treatment with a bispecific antibody (bsAb) comprised of an anti-EGFR v-region paired with LIGHT, increased immune infiltrate leading to potent anti-tumor activity in models resistant to PD-1 blockade (Tang, H., et al., 2016, Cancer Cell, 30:500). TLS neogenesis may provide advantages over specific immune cell subset immunotherapies (e.g. T cell redirection), since it leads to infiltration of a diverse immune repertoire, including both innate and adaptive immune cells, that is more likely to overcome immune resistance.093699.0207 PATENT Several groups have targeted LTβR using its natural ligands LIGHT and LTα1β2 (Tang, H., et al., 2016, Cancer Cell, 30:500, Yu, P., et al., 2004, Nat Immunol, 5:141-149; Yu, P., et al., 2007, J Immunol, 179:1960-1968; Johansson-Percival, A., et al., 2017, Nat Immunol, 18:1207- 1217; Gurney et al. WO2018 / 119118). Whereas LTα1β2 is specific for LTβR, LIGHT also binds to and activates HVEM / TNFRSF14, a receptor expressed on and implicated in the regulation of immune cells (Pasero, C., et al., 2012, Curr Opin Pharmacol, 12:4778-485). LTβR-dependent downstream signaling can be initiated independently of ligand binding, either by receptor overexpression leading to self-association (Ganeff, C., et al., 2011, Mol Cell Biol, 31:4319-4334; Dhawan, P., et al., 2008, J Biol Chem, 283:15399-15408; Wu, M. Y., et al., 1999, J Biol Chem, 274:11868-11873), or artificially by anti-LTβR agonistic antibodies that induce receptor aggregation (Mackay, F., et al., 1996, J Biol Chem, 271:24934-24938; VanArsdale, T. L., et al., 1997, Proc Natl Acad Sci USA, 94:2460-2465). Due to the broad expression of LTβR, an agonistic LTβR-targeting drug capable of inducing signaling and creating an activating immune environment bears a substantial risk of causing systemic immune-related adverse events. Johansson-Percival et al. reported weight loss in mice after systemic administration of an LTβR activating compound, VTP-LIGHT (Johansson- Percival et al., Nat. Immunol. 18:1207-17 (2017)). Therefore, a therapeutic modality which activates LTβR specifically in the tumor but not in other tissues is needed to reduce the risk of toxicity and to generate a well-tolerated drug that can be employed for combination therapies. Typically, scFv domains recognizing a cell surface-exposed tumor antigen or tumor stroma antigen are used as anchor domain, but the suitability of other types of protein domains has been demonstrated as well (de Bruyn, M., et al., 2013, Cancer Lett, 332:175-183; Wajant, H., et al., 2013, Cancer Lett, 332:163-174; Wajant, H., et al., 2019, Cancers, 11(7):954). The use of an appropriate anchor domain allows the generation of fusion proteins which not only ensure full activation of TNFRSFs but also do this in a local fashion and / or link it with a second activity. The present invention meets this long felt, but unmet need. BRIEF SUMMARY OF THE INVENTION In certain embodiments, the presently disclosed subject matter relates to a multispecific binding molecule including a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof. In certain embodiments, the binding domain that specifically binds to LTβR includes a heavy chain variable region (VH) and a light chain variable region (VL) including: (a) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2093699.0207 PATENT including the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 698; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 701; (b) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 762, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 763; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 730; (c) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 770; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 773; (d) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 798; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 801; or (e) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 727; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 767. In certain embodiments, the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 698; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 701. In certain embodiments, the VH includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ093699.0207 PATENT ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO: 511. In certain embodiments, the VL includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO: 513. In certain embodiments, the VH includes the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO: 511. In certain embodiments, the VL includes the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO: 513. In certain embodiments, the VH includes the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO: 511; and the VL includes the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO: 513. In certain embodiments, (a) the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 251; (b) the VH includes the amino acid sequence set forth in SEQ ID NO: 473 and the VL includes the amino acid sequence set forth in SEQ ID NO: 474; (c) the VH includes the amino acid sequence set forth in SEQ ID NO: 4 and the VL includes the amino acid sequence set forth in SEQ ID NO: 5; (d) the VH includes the amino acid sequence set forth in SEQ ID NO: 4 and the VL includes the amino acid sequence set forth in SEQ ID NO: 29; (e) the VH includes the amino acid sequence set forth in SEQ ID NO: 473 and the VL includes the amino acid sequence set forth in SEQ ID NO: 496; (f) the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 273; (g) the VH includes the amino acid sequence set forth in SEQ ID NO: 34 and the VL includes the amino acid sequence set forth in SEQ ID NO: 33; (h) the VH includes the amino acid sequence set forth in SEQ ID NO: 278 and the VL includes the amino acid sequence set forth in SEQ ID NO: 277; (i) the VH includes the amino acid sequence set forth in SEQ ID NO: 501 and the VL includes the amino acid sequence set forth in SEQ ID NO: 500; (j) the VH includes the amino acid sequence set forth in SEQ ID NO: 44 and the VL includes the amino acid sequence set forth in SEQ ID NO: 46; (k) the VH includes the amino acid sequence set forth in SEQ ID NO: 288 and the VL includes the amino acid sequence set forth in093699.0207 PATENT SEQ ID NO: 290; (l) the VH includes the amino acid sequence set forth in SEQ ID NO: 511 and the VL includes the amino acid sequence set forth in SEQ ID NO: 513; (m) the VH includes the amino acid sequence set forth in SEQ ID NO: 32 and the VL includes the amino acid sequence set forth in SEQ ID NO: 33; (n) the VH includes the amino acid sequence set forth in SEQ ID NO: 276 and the VL includes the amino acid sequence set forth in SEQ ID NO: 277; or (o) the VH includes the amino acid sequence set forth in SEQ ID NO: 499 and the VL includes the amino acid sequence set forth in SEQ ID NO: 500. In certain embodiments, the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 251. In certain embodiments, the binding domain that specifically binds to LTβR includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226. In certain embodiments, the binding domain that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226. In certain embodiments, the binding domain that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2197. In certain embodiments, the binding domain that specifically binds to EDB or a fragment or derivative thereof includes a heavy chain variable region (VH) and a light chain variable region (VL) including an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 704; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 707. In certain embodiments, the binding domain that specifically binds to EDB includes a heavy chain variable region (VH) including an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 6. In certain embodiments, the binding domain that specifically binds to EDB includes a light chain variable region (VL) including an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the binding domain that specifically binds to EDB includes a VH including the amino acid sequence set forth in SEQ ID NO: 6. In certain embodiments, the binding domain that specifically binds to EDB includes a VL including the093699.0207 PATENT amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the binding domain that specifically binds to EDB includes a VH including the amino acid sequence set forth in SEQ ID NO: 6 and a VL including the amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the multispecific binding molecule is a bispecific antibody. In certain embodiments, the presently disclosed subject matter relates to a multispecific binding molecule including a first heavy chain (HC1), a first light chain (LC1), a second heavy chain (HC2), and a second light chain (LC2). In certain embodiments, the HC1 is fused to a first antigen-binding fragment that specifically binds to LTβR and the HC2 is fused to a second antigen- binding fragment that specifically binds to LTβR. In certain embodiments, (a) each of the HC1 and HC2 includes a heavy chain variable region (VH) including an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 704; (b) each of LC1 and LC2 includes a light chain variable region (VL) including an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 707; and (c) each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR includes a heavy chain variable region (VH) and a light chain variable region (VL) including: (i) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 698; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 701; (ii) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 762, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 763; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 730; (iii) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 770; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 773; (iv) the VH includes an HCDR1 including the093699.0207 PATENT amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 798; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 801; or (v) the VH includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 727; and the VL includes an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 767. In certain embodiments, each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR includes an HCDR1 including the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 including the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 including the amino acid sequence set forth in SEQ ID NO: 698, an LCDR1 including the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 including the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 including the amino acid sequence set forth in SEQ ID NO: 701. In certain embodiments, each of the HC1 and HC2 includes a VH including the amino acid sequence set forth in SEQ ID NO: 6. In certain embodiments, each of the LC1 and LC2 includes a VL including the amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR includes: (a) the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 251; (b) the VH includes the amino acid sequence set forth in SEQ ID NO: 473 and the VL includes the amino acid sequence set forth in SEQ ID NO: 474; (c) the VH includes the amino acid sequence set forth in SEQ ID NO: 4 and the VL includes the amino acid sequence set forth in SEQ ID NO: 5; (d) the VH includes the amino acid sequence set forth in SEQ ID NO: 4 and the VL includes the amino acid sequence set forth in SEQ ID NO: 29; (e) the VH includes the amino acid sequence set forth in SEQ ID NO: 473 and the VL includes the amino acid sequence set forth in SEQ ID NO: 496; (f) the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 273; (g) the VH includes the amino acid sequence set forth in SEQ ID NO: 34 and the VL includes the amino acid sequence set forth in SEQ ID NO: 33; (h) the VH includes the amino acid sequence set forth in SEQ ID NO: 278 and the VL includes the amino acid sequence set forth in093699.0207 PATENT SEQ ID NO: 277; (i) the VH includes the amino acid sequence set forth in SEQ ID NO: 501 and the VL includes the amino acid sequence set forth in SEQ ID NO: 500; (j) the VH includes the amino acid sequence set forth in SEQ ID NO: 44 and the VL includes the amino acid sequence set forth in SEQ ID NO: 46; (k) the VH includes the amino acid sequence set forth in SEQ ID NO: 288 and the VL includes the amino acid sequence set forth in SEQ ID NO: 290; (l) the VH includes the amino acid sequence set forth in SEQ ID NO: 511 and the VL includes the amino acid sequence set forth in SEQ ID NO: 513; (m) the VH includes the amino acid sequence set forth in SEQ ID NO: 32 and the VL includes the amino acid sequence set forth in SEQ ID NO: 33; (n) the VH includes the amino acid sequence set forth in SEQ ID NO: 276 and the VL includes the amino acid sequence set forth in SEQ ID NO: 277; or (o) the VH includes the amino acid sequence set forth in SEQ ID NO: 499 and the VL includes the amino acid sequence set forth in SEQ ID NO: 500. In certain embodiments, each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR includes the VH includes the amino acid sequence set forth in SEQ ID NO: 250 and the VL includes the amino acid sequence set forth in SEQ ID NO: 251. In certain embodiments, each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR is a stapled single chain Fv (spFv). In certain embodiments, the spFv includes the amino acid sequence set forth in SEQ ID NO: SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226. In certain embodiments, the spFv includes the amino acid sequence set forth in SEQ ID NO: SEQ ID NO: 2197. In certain embodiments, each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2174. In certain embodiments, each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2174. In certain embodiments, each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2105 or 2486. In certain embodiments, each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2093699.0207 PATENT fused to the second antigen-binding fragment that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2105 or 2486. In certain embodiments, each of the LC1 and LC2 includes an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, each of the LC1 and LC2 includes the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, (a) each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2174; and (b) each of the LC1 and LC2 includes the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, (a) each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR includes the amino acid sequence set forth in SEQ ID NO: 2105 or 2486; and (b) each of the LC1 and LC2 includes the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, the multispecific binding molecule is a bispecific antibody. In certain embodiments, the presently disclosed subject matter relates to a multispecific binding molecule including (a) a first polypeptide that specifically binds to LTβR and EDB; (b) a second polypeptide that specifically binds to EDB; (c) a third polypeptide that specifically binds to LTβR and EDB; (d) a fourth polypeptide that specifically binds to EDB; wherein each of the first polypeptide and the third polypeptide includes the amino acid sequence set forth in SEQ ID NO: 2174, and wherein each of the second polypeptide and the fourth polypeptide includes the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, the presently disclosed subject matter relates to a multispecific binding molecule including (a) a first polypeptide that specifically binds to LTβR and EDB; (b) a second polypeptide that specifically binds to EDB; (c) a third polypeptide that specifically binds to LTβR and EDB; (d) a fourth polypeptide that specifically binds to EDB; wherein each of the first polypeptide and the third polypeptide includes the amino acid sequence set forth in SEQ ID NO: 2105 or 2486, and wherein each of the second polypeptide and the fourth polypeptide includes the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, the multispecific binding molecule is a bispecific antibody. In certain embodiments, the presently disclosed subject matter relates to a nucleic acid molecule encoding the multispecific binding molecule disclosed herein. In certain embodiments, the presently disclosed subject matter relates to a vector including the nucleic acid molecule093699.0207 PATENT disclosed herein. In certain embodiments, the presently disclosed subject matter relates to a host cell including the nucleic acid molecule or the vector disclosed herein. In certain embodiments, the presently disclosed subject matter relates to a composition including the multispecific binding molecule disclosed herein. In certain embodiments, the composition is a pharmaceutical composition further including a pharmaceutically acceptable carrier. In certain embodiments, the presently disclosed subject matter relates to a method of producing a multispecific binding molecule, the method comprising culturing the host cell disclosed herein; and (b) harvesting the molecule. In certain embodiments, the presently disclosed subject matter relates to a method of treating cancer in a subject in need thereof, activating non-canonical NF-κB signaling in a subject in need thereof, and / or inducing tertiary lymphoid structure (TLS) neogenesis in a subject in need thereof. In certain embodiments, the method comprises administering to the subject an effective amount of the multispecific binding molecule, the nucleic acid molecule, the vector, or the composition disclosed herein. In certain embodiments, the method further includes administering a second therapeutic agent selected from the group consisting of an anti-CD20 mAb, an anti-TIM- 3 mAb, an anti-CTLA-4 antibody, an anti-PD-L1 antibody, an anti-PD-1 antibody, a PD-1 / PD-L1 therapy, Indoleamine-pyrrole 2,3-dioxygenase (IDO), an anti-OX40 antibody, an anti-GITR antibody, an anti-CD40 antibody, an anti-CD38 antibody, a cytokine, an oncolytic virus, a TLR agonist, a STING agonist, and combinations thereof. In certain embodiments, the cancer is a lung cancer, a bladder cancer, a head and neck cancer, an esophageal cancer, a vaginal cancer, a pancreatic cancer, a colon cancer, a liver cancer, uterine cancer, an ovarian cancer, a breast cancer, a prostate cancer, a stomach cancer, a melanoma, a glioblastoma (GBM), an endometrial cancer, a soft tissue carcinoma, or a mesothelioma. In certain embodiments, the lung cancer is a small cell lung cancer, a non small cell lung cancer (NSCLC), an adenocarcinoma, a squamous lung cancer and / or carcinoma, or a large cell carcinoma. In certain embodiments, the bladder cancer is a urinary bladder cancer, a metastatic bladder cancer, a muscle invasive bladder cancer, or a non-invasive bladder cancer. In certain embodiments, the head and neck cancer is a pharynx cancer, a larynx cancer, or an oral cavity cancer. In certain embodiments, the cancer is an esophageal cancer. In certain embodiments, the vaginal cancer is a cancer of the vulva, a cancer of the vagina, or a cancer of the cervix. In certain embodiments, the cancer is a pancreatic cancer. In certain embodiments, the cancer is a colon cancer, a colorectal cancer, a cancer of the small intestines, a gastrointestinal cancer, or a rectal093699.0207 PATENT cancer. In certain embodiments, the cancer is an EDB-expressing cancer or a cancer with a high prevalence of EDB expression. BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of embodiments of the invention will be better understood when read in conjunction with the appended drawings. It should be understood that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. Figure 1, comprising Figure 1A through Figure 1O, depicts representative schematics of various antibody formats. Figure 1A depicts a schematic of a doubly conjugated Morrison-type antibody with two scFvs conjugated to the C-terminus of the Fc domain (Coloma MJ, Morrison SL. Design and Production of Novel Tetravalent Bispecific Antibodies. Nat. Biotechnol. 15(2) 2011:159–163; doi:10.1038 / nbt0297-159). Figure 1B depicts a schematic of a singly conjugated Morrison-type antibody with one scFv conjugated to the C-terminus of the Fc domain of a single heavy chain. Figure 1C depicts a schematic of a monovalent singly conjugated Morrison-type antibody with one Fc region and a single scFv conjugated to the C-terminus of the full-length heavy chain. Figure 1D depicts a schematic representation of a doubly conjugated monovalent Morrison- type antibody with one scFv conjugated to the C-terminus of the Fc and one scFv conjugated to the C-terminus of the full-length heavy chain. Figure 1E depicts a schematic of a doubly conjugated Morrison-type antibody with two scLIGHT trimers conjugated to the C-terminus of the Fc domain. Figure 1F depicts a schematic of a singly conjugated Morrison-type antibody with one scLIGHT trimer conjugated to the C-terminus of the Fc domain of a single heavy chain. Figure 1G depicts a schematic of a monovalent singly conjugated Morrison-type antibody with one Fc region and a single scLIGHT trimer conjugated to the C-terminus of the full-length heavy chain. Figure 1H depicts a schematic of a doubly conjugated monovalent Morrison-type antibody with one scLIGHT trimer conjugated to the C-terminus of the Fc and one scLIGHT trimer conjugated to the C- terminus of the full-length heavy chain. Figure 1I depicts a schematic of a doubly conjugated Fab antibody with an scFv conjugated to the N-terminus of each heavy chain. Figure 1J depicts a schematic of a singly conjugated monovalent antibody with an Fc and a single scFv conjugated to the N-terminus of the full-length heavy chain. Figure 1K depicts schematic of a monovalent antibody with a single scLIGHT trimer conjugated to the N-terminus of the Fc chain. Figure 1L depicts a schematic of a “wedged” bivalent antibody with a single scFv inserted between the C- terminus of a VH domain and the N-terminus of the Fc chain. Figure 1M depicts a schematic of a093699.0207 PATENT monovalent antibody with a single scFv fused to the N-terminus of an Fc chain. Figure 1N depicts a schematic of an scFv. Figure 1O depicts a schematic of a monoclonal antibody. Figure 2 depicts representative results of an E. coli-based evaluation of the anti-LTβR v- region in scFv format. The graph shows the magnitude of the ELISA response on the y-axis for the binding by the E9 scFv formatted as VL-linker-VH (LTΒRB132) or as VH-linker-VH (LTΒRB131). The negative controls included were an scFv (F5) that is known to form a stable scFv but does not bind LTβR and a media only control. Bars indicate the binding response after heat treatment at the indicated temperature. Figure 3, comprising Figure 3A through Figure 3C, depicts representative illustrations for hydrogen-deuterium exchange (HDX) based epitope mapping of the interaction between anti- LTβR E9 v-region or LIGHT, and LTβR. Figure 3A depicts a cartoon illustration of a model for the binding between LTβR and LIGHT based on PDB ID 4MXW and PDB ID 4J6G showing the two N-terminal CRDs in LTβR are primarily responsible for binding LIGHT. Figure 3B depicts representative maps of the HDX-derived epitope map of residues in LTβR that interact with either the E9 v-region (left) or LIGHT (right). Figure 3C depicts the residues in LTβR that interact with either the anti-LTβR E9 scFv (solid lines) or LIGHT (dashed lines) as indicated beneath the sequence of LTβR. Indicated domain boundaries are from Uniprot. The primary epitopes (thick lines) indicate residues whose HD-exchange rate were significantly altered upon binding and the secondary epitope (thin lines) indicate residues whose HD-exchange rate was modestly affected by binding. SEQ ID NO: 2477 is featured in Figure 3C. Figure 4 depicts a representative sequence alignment of the extracellular domain of LTβR in human, cynomolgus monkey, rat, and mouse. Residues that interact with the E9 v-region are highlighted in gray boxes. H.s. = Homo sapiens, M.f. = macaca fascicularis, R.n. = Rattus norvegicus, M.m. = Mus musculus. SEQ ID Nos: 2478-2481 are featured in Figure 4. Figure 5, comprising Figure 5A and Figure 5B, depicts representative HDX-based epitope mapping of the interaction between anti-EDB L19 v-region and EDB. Figure 5A depicts a representative map of the HDX-derived epitope map of residues in EDB that interact with the anti- EDB L19 v-region (sticks) shown on the FNIII-7-EDB-FNIII-8 structure (PDB ID 3T1W). Figure 6B depicts a representation of the residues in fibronectin that interact with the anti-EDB L19 v- region as indicated beneath the sequence of fibronectin. Indicated domain boundaries are from Uniprot. The primary epitopes (thick lines) indicate residues whose HD-exchange rate were significantly altered upon binding and the secondary epitope (thin lines) indicate residues whose HD-exchange rate was modestly affected by binding. SEQ ID NO: 2475 is featured in Figure 5B.093699.0207 PATENT Figure 6 depicts a representative sequence alignment of the fibronectin ED-B in human, cynomolgus monkey, rat, and mouse. Residues that interact with the anti-EDB L19 v-region are underlined. Thick lines indicate the major epitope and thin line indicates the minor epitope, based on HD-exchange MS. H.s. = Homo sapiens, M.f. = macaca fascicularis, R.n. = Rattus norvegicus, M.m. = Mus musculus. SEQ ID Nos: 2482-2485 are featured in Figure 6. Figure 7 depicts representative binding of MSLN × LTβR bispecific antibodies to human MSLN-expressing HGC27 and CT26-huMSLN cells, and MSLN-negative MCF-7 and CD26 cells, of which only HGC27 do not express LTβR. Receptor density data for MSLN and LTβR for these cell lines are listed in Table 14. Depicted are representative flow cytometry results of the dose range binding, represented by Alexa Fluor 488 (AF488) Geomean values, of MSLN × LTβR (MSLN-bivalent × LTβR-monovalent, LTBRB44; MSLN-bivalent × LTβR-bivalent, LTBRB145; MSLN-monovalent × LTβR-bivalent, LTBRB305) and the corresponding α-RSV × LTβR control antibodies (α-RSV-bivalent × LTβR-monovalent, LTBRB9; α-RSV-bivalent × LTβR-bivalent, LTBRB387), detected by AF488-labeled secondary anti-human Fc antibody. Figure 8, comprising Figure 8A and Figure 8B, depicts representative luciferase reporter assay results demonstrating the activation of NF-κB pathways by MSLN-bivalent × LTβR-bivalent (LTBRB145) compared to MSLN-bivalent × LTβR-monovalent (LTBRB383) and MSLN- monovalent × LTβR-bivalent (LTBRB305) bispecific antibodies and corresponding controls (α- RSV-bivalent × LTβR-monovalent, LTBRB9; α-RSV-bivalent × LTβR-bivalent, LTBRB387). Figure 8A depicts representative NF-κB activation, shown by fold induction of luminescence signal normalized to untreated control, when MSLN-expressing NCI-H596 cells were co-cultured with A549 NF-κB-luc reporter cells and stimulated for 16-20 hours by dose range of antibodies. Figure 8B depicts representative NF-κB activation, shown by fold induction of luminescence signal normalized to untreated control, when A549 NF-κB-luc reporter cells were stimulated for 16-20 hours by dose range of antibodies in the absence of MSLN-expressing cells. Figure 9, comprising Figure 9A and Figure 9B, depicts representative luciferase reporter assay results demonstrating the NF-κB activation in murine NIH / 3T3 NF-κB-luc reporter cells, by MSLN × LTβR and corresponding control α-RSV × LTβR. Figure 9A depicts representative NF- κB activation in NIH / 3T3 NF-κB-luc reporter cells (shown as fold induction of luciferase signal normalized to untreated control) cultured for 16-20 hours in the presence or absence of CT26 cells engineered to express human MSLN, by MSLN-bivalent × LTβR-bivalent antibody (LTBRB145) compared to corresponding control (α-RSV × LTβR, LTBRB387). Figure 9B depicts representative results demonstrating the NF-κB activation in NIH / 3T3 NF-κB-luc reporter cells cultured for 16-20 hours in the presence or absence of CT26 cells engineered to express human093699.0207 PATENT MSLN, by MSLN-bivalent × LTβR-monovalent antibody (LTBRB383) compared to corresponding control (α-RSV × LTβR, LTBRB381). Figure 10, comprising Figure 10A and Figure 10B, depicts representative luciferase reporter assay results demonstrating the activation of NF-κB pathways in A549 NF-κB-luc reporter cells at 16-20 hours of stimulation with MSLN × LTβR bispecific antibodies, including antibodies with Fc modifications that enhance clustering (RE). Figure 10A demonstrates the activation of NF- κB pathways in A549 NF-κB-luc reporter cells when co-cultured with MSLN-expressing NCI- H596 cells (shown as fold induction of luciferase signal normalized to untreated control) by MSLN × LTβR bispecific antibodies with RE modifications (MSLN-monovalent × LTβR-bivalent, LTBRB313; MSLN-bivalent × LTβR-bivalent, LTBRB148; MSLN-monovalent × LTβR- monovalent, LTBRB346; MSLN-bivalent × LTβR-monovalent, LTBRB169) compared to antibodies lacking the modifications (MSLN-monovalent × LTβR-bivalent, LTBRB305; MSLN- bivalent × LTβR-bivalent, LTBRB145; MSLN-monovalent × LTβR-monovalent, LTBRB338; and MSLN-bivalent × LTβR-monovalent, LTBRB383, respectively). Figure 10B depicts the activation of NF-κB pathways in A549 NF-κB-luc reporter cells when cultured alone or co-cultured with MSLN-expressing NCI-H596 cells (shown as fold induction of luciferase signal normalized to untreated control) by MSLN × LTβR RE-based Fc modified (LTBRB148, top panel) and unmodified (LTBRB145, middle panel), respectively, and rhLIGHT (bottom panel). Maximal fold induction and EC50for co-culture setting are indicated on the graphs. Figure 11, comprising Figure 11A and Figure 11B, depicts representative luciferase reporter assay results demonstrating NF-κB activation in A549 NF-κB-luc reporter cells culturedin in huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated plates , as a fold induction in luminescencesignal normalized to unstimulated control, by α-EDB-bivalent antibody-LIGHT fusion protein (LTBRB162) and EDB-bivalent × LTβR-monovalent (LTBRB384) and EDB-bivalent × LTβR- bivalent (LTBRB146) antibodies. Figure 11A depicts representative experimental results demonstrating NF-κB signaling induction in A549 NF-κB-luc reporter cells cultured for 16-20 hours by EDB × LTβR antibodies (LTBRB146 and LTBRB384) and their respective controls (α- RSV × LTβR, LTBRB381 and LTBRB387, respectively). Figure 11B depicts representative experimental results comparing NF-κB signaling induction with EDB × LTβR antibody (LTBRB146) and α-EDB × LIGHT fusion protein (LTBRB162), and their respective controls (α- RSV × LTβR, LTBRB387 and α-RSV × LIGHT, LTBRB162) in A549 NF-κB-luc reporter cells cultured for 16-20 hours. Figure 12 depicts representative luciferase reporter assay results demonstrating the time kinetics of NF-κB activation (represented by fold induction of luminescence signal normalized to093699.0207 PATENT unstimulated control) in A549 NF-κB-luc reporter cells cultured in huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated plates, by EDB-bivalent × LTβR-bivalent antibody (LTBRB146), EDB- bivalent × LTβR-monovalent antibody (LTBRB384), α-EDB bivalent antibody-LIGHT fusion protein (LTBRB162) and α-EDB-bivalent × antibody-LTα1b2 fusion protein (LTBRB137) after 30 min, 1 hour, 2 hours, 4 hours and 6 hours stimulation. Figure 13 depicts representative results of the NF-κB non-canonical pathway (p100 and p52) activation in A549 cells, analyzed by JESS capillary Western blotting. Graph shows ratio between p52 and p100 protein area, normalized to unstimulated control cells, at indicated time points after stimulation with 20 ng / ml of TNF-α, EDB-bivalent × LTβR-bivalent antibody (LTBRB146, 10 nM) and α-EDB antibody-LIGHT fusion protein (LTBRB162, 10 nM). Figure 14 depicts representative results of the NF-κB non-canonical (p100 and p52, top panel) and canonical (phospho-p65, middle panel and phospho-IkBα, bottom panel) pathways activation in A549 cells, analyzed by JESS capillary Western blotting. The results are demonstrated as a ratio between p52 and p100 protein area (top panel), phosphor-p65 (middle panel) and a ratio between phospho-IkBα and total IkBα protein (bottom panel), all normalized to unstimulated control cells, at 4 hours after stimulation with various concentrations of TNF-α (right), EDB- bivalent × LTβR-bivalent antibody (LTBRB509), α-EDB antibody-LIGHT fusion protein (LTBRB162), EDB-bivalent × LTβR monovalent antibody (LTBRB384) and α-EDB × LTα1b2 fusion protein (LTBRB137)(left). Figure 15, comprising Figure 15A through Figure 15C, depicts representative results of cytokine release induction (interleukin 6 (IL-6), Figure 15A; interferon gamma-induced protein- 10 (IP-10), Figure 15B; and interferon-inducible T-cell alpha chemoattractant (ITAC), Figure 15C) in WI-38-132RA co-cultured with A375 for 24 hours by EDB × LTβR antibodies (LTBRB146 and LTBRB384) and their respective controls (α-RSV × LTβR, LTBRB381 and LTBRB387), and α- EDB antibody-LIGHT fusion protein (LTBRB162) and its control (α-RSV antibody-LIGHT, LTBRB29). Figure 16 depicts representative time course profiles of monocyte transmigration under flow through monolayer of pre-activated human umbilical vein endothelial cell (HUVEC) cultured on huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated microscope flow chamber slide. HUVEC cells were pre-activated for 1 day with EDB-bivalent × LTβR antibodies, α-EDB antibody-LIGHT fusion protein (filled symbols, LTBRB146, LTBRB384, and LTBRB162, left, middle, and right, respectively) or control α-RSV × LTβR antibodies or α-RSV antibody-LIGHT fusion protein (LTBRB387, LTBRB381, and LTBRB29, left, middle, and right, respectively). Monocytes were flowed over activated HUVECs for 6 minutes, followed by a 50-minutes co-culture step with wash093699.0207 PATENT buffer, where monocytes were individually tracked and their positions marked at 1-minute intervals. Transmigration events were captured and counted per unit field. All experiments were carried out using triplicate fields and presented as a mean value with ± standard error measurements (± SEM). Figure 17 depicts representative results of a monocyte transmigration flow assay (described in Figure 16) demonstrating individual EC50 profiles for EDB-bivalent × LTβR antibodies, α-EDB antibody-LIGHT fusion protein (filled symbols, LTBRB146, LTBRB384, and LTBRB162, left, middle, and right, respectively) or control α-RSV × LTβR antibodies or α-RSV antibody-LIGHT fusion protein (LTBRB387, LTBRB381, and LTBRB29, left, middle, and right, respectively) using AUC summary values of monocyte capture and transmigration. Profiles and non-linear fit calculated using GraphPad Prism 9.0 (Function: [Agonist] vs. response – variable slope). Figure 18 depicts representative effects of LTBRB401 (EDB-bivalent × LTβR-bivalent muIgG2a-AAS bispecific antibody) treatment either as monotherapy or in combination with α-PD- 1 antibody (clone RMP1-14) on growth of subcutaneous CT26 murine tumors. Group tumor volumes are graphed as the mean ± SEM (n = 10 mice / group). CT26 tumor cells were implanted on Day 0 (group mean tumor volumes 75 - 77 mm3), followed by biweekly treatment (intraperitoneally, IP) starting on Day 13 for total of 8 doses. Figure 19 depicts representative effects of LTBRB398 (EGFR-bivalent × LTβR-bivalent muIgG2a-AAS bispecific antibody) treatment either as monotherapy or in combination with α-PD- 1 antibody (clone RMP1-14) on growth of subcutaneous human EGFR-expressing CT26 (CT26- huEGFR) murine tumors. Group tumor volumes are graphed as the mean ± SEM (n=20 mice / group). CT26-huEGFR tumor cells were implanted on Day 0 (group mean tumor volumes 65.9-66.5 mm3), followed by biweekly treatment (intraperitoneally, IP) starting on Day 10 for total of 10 doses. Figure 20, comprising Figure 20A and Figure 20B, depicts representative effects of MSLN × LTβR muIgG2a-AAS bispecific antibodies treatment either as monotherapy or in combination with α-PD-1 antibody (clone RMP1-14) on growth of subcutaneous human MSLN-expressing murine tumors. Figure 20A depicts representative effects of LTBRB399 (MSLN-bivalent × LTβR- bivalent muIgG2a-AAS bispecific antibody) treatment either as monotherapy (at 10 mg / kg and 20 mg / kg IP) or in combination with α-PD-1 antibody (clone RMP1-14) on growth of subcutaneous human MSLN-expressing MC38 (MC38-huMSLN) murine tumors. Group tumor volumes are graphed as the mean ± SEM (n=10 mice / group). MC38-huMSLN tumor cells were implanted on Day 0 (group mean tumor volumes 66 and 67 mm3), followed by biweekly treatment (intraperitoneally, IP) starting on Day 13 for total of 8 doses. Figure 20B depicts representative effects of LTBRB399 (MSLN-monovalent × LTβR-bivalent muIgG2a-AAS bispecific antibody),093699.0207 PATENT LTBRB459 (MSLN-monovalent × LTβR-bivalent muIgG2a-AAS) and LTBRB435 (MSLN- monovalent × LTβR-monovalent muIgG2a-RE-AAS) bispecific antibodies treatment on growth of subcutaneous human MSLN-expressing CT26 (CT26-huMSLN) murine tumors. Group tumor volumes are graphed as the mean ± SEM (n=10 mice / group). CT26-huMSLN tumor cells were implanted on Day 0 (group mean tumor volumes 22 and 30 mm3), followed by biweekly treatment (intraperitoneally, IP) starting on Day 11 for total of 6 doses. Figure 21 shows a graphical representation of the AGB201 molecule. Figures 22A and 22B depict the binding rate curves of the tested antibodies using Octet platform. Figures 23A and 23B illustrate the binding activity of the AGB201 molecule. Figure 23A shows the binding to LTβR+A549 cells. Figure 23B shows the SPR binding spectra of the AGB201 molecule to recombinant LTβR. Figures 24A and 24B show HDX-MS epitope mapping of huFn-7-EDB-8-9 (EDB+) against AGB201 overlaid on an X-ray crystal structure (3T1W). The paratope map of LTBRW3 against LTBRB509 shows the free energy change upon binding to an mAb which is depicted in gradient color from red to blue as shown on the right. The residues which are shown from blue to green are the HDX-MS identified epitopes. The residues which were not stabilized upon binding to the antibodies were shown yellow. The residues that exchange too fast or too slow to see the perturbation upon the binding were shown gray. The residues without color indicate the HDX behaviors were not monitored, because there is no peptide to cover the residues, or the residues are the first two residues of a peptide. G indicates a glycosylation site. SEQ ID NO: 2488 is featured in Figure 24A. Figures 25A-25E illustrate the binding properties of the AGB201 molecule. Figure 25A shows Retrogenix images and quantitation from pre-screen. Briefly, 2 mg / mL of AGB201, 1 μg / mL of Rituximab biosimilar or PBS alone, was added to fixed untransfected HEK293 cells (non-spotted areas) or cells over-expressing FN1, LTBR or CD20 (spotted areas). Levels of background binding of the test and control antibodies to untransfected HEK293 cells, relative to untransfected cells treated with PBS / secondary alone, were quantitated (numeric values are shown alongside each image). Figure 25B shows dose-related binding of AGB201 to LTBR and FN1 (EDB) transfected HEK293 cells. Figure 25C depicts FACS profiles where each graph shows the level of binding of a dose range (0.018 – 300 mg / mL) of AGB201, or secondary detection antibody alone to HEK293 cells transiently transfected with ZsGreen1-only (“ZsHek”; negative control), or ZsGreen1 and each target (LTBR, FN1 [EDB]). Figure 25D shows FACS profiles, wherein each graph shows the level of binding of a dose range (0.018 – 300 mg / mL) of AGB201, or secondary093699.0207 PATENT detection antibody alone to CHOK1 cells transiently transfected with ZsGreen1-only (“ZsHek”; negative control), or ZsGreen1 and each target (LTBR, FN1 [EDB]). Figure 25E shows dose- related binding of AGB201 to LTBR and FN1 (EDB) transfected CHOK1 cells. Data for Figures 25A-25C were obtained using HEK293 transfected cells. Data for Figures 25D and 25E were obtained using CHOK1 transfected cells. Figure 26A-26D illustrate the pharmacokinetics of the AGB201 molecule. Figure 26A shows a graph based on AGB201 CD1 EBD capture experiments. Figure 26B shows a graph based on multi-dose AGB201 CD1 EDB capture experiments. Figure 26C shows a graph based on nullxEDB vs AGB201: CD1 EBD capture experiments. Figure 26D shows a graph based on AGB201 CD1 TLBR and EDB capture experiments. Figures 27A-27C illustrate data obtained from simian models. Figure 27A shows a pharmacokinetics analysis of Cambodian cynomolgus monkeys administered with AGB201. Figure 27B shows an immunophenotyping analysis of Cambodian cynomolgus monkeys administered with AGB201. Figure 27C shows the cytokine analysis of Cambodian cynomolgus monkeys administered with AGB201. Figures 28A and 28B depict cytokine induction in CD1 mice treated with AGB201. Figure 28A shows the boxplots of the logarithm of the predilution-adjusted back-calculated concentration (pg / ml) by cytokine, predilution, censoring type, and group. Cytokines CCL19 / MIP-3b and CCL5 / RANTES had limited valid observations (most of the data are censored). Therefore, no statistical modeling was done for these two cytokines. The 100 mg / kg on Day 02 and 100 mg / kg on Day 26 for the cytokine CXCL12 / SDF-1a were also not included in the analysis as these groups were fully censored. Figure 28B shows the graph of the plasma sample concentrations. Vehicle control group readings were below the detection limit of standards used to calculate the plasma LTBR levels. Figure 29 shows toxicokinetics in CD1 mice treated with AGB201. Mean (SD) whole blood LTBRB509 concentration-time profiles following twice weekly IV bolus doses of LTBRB509 in female CD-1®IGS mice. Figures 30A-30 depict the effects of LTBR146 on NF-kB pathways. Figure 30A shows an immunoblotting analysis of canonical and non-canonical NF-kB pathways activated by LTBR146. Figure 30B depicts representative results of the NF-^B non-canonical pathway (p100 and p52) activation in A549 cells, analyzed by JESS capillary Western blotting. The graph shows the ratio between p52 and p100 protein area, normalized to unstimulated control cells, at indicated time points after stimulation with 20 ng / ml of TNF-^ EDB-bivalent × LT^R-bivalent antibody (LTBRB146, 10 nM) and ^-EDB × LIGHT fusion protein (LTBRB162, 10 nM). Figure 30C093699.0207 PATENT depicts representative results of the NF-^B non-canonical (p100 and p52, top panel) and canonical (phospho-p65, middle panel and phospho-IkBα, bottom panel) pathways activation in A549 cells, analyzed by JESS capillary Western blotting. The results are demonstrated as a ratio between p52 and p100 protein area (top panel), phosphor-p65 (middle panel), and a ratio between phospho-IkBα and total IkBα protein (bottom panel), all normalized to unstimulated control cells, at 4 hours after stimulation with various concentrations of TNF-^ (right), EDB-bivalent × LT^R-bivalent antibody (LTBRB509), ^-EDB × LIGHT fusion protein (LTBRB162), EDB-bivalent x LT^R monovalent antibody (LTBRB384) and ^-EDB x LT^1^2 fusion protein (LTBRB137). Figures 31A-31E show the effects of LTBR146 on NF-^B pathways. Figure 31A depicts representative luciferase reporter assay results demonstrating the time kinetics of NF-^B activation (represented by fold induction of luminescence signal normalized to unstimulated control) in A549 NF-^B-luc reporter cells cultured in huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated plates, by EDB- bivalent × LT^R-bivalent antibody (LTBRB146), EDB-bivalent × LT^R-monovalent antibody (LTBRB384), ^-EDB bivalent × LIGHT fusion protein (LTBRB162) and ^-EDB-bivalent x LT^1^2 fusion protein (LTBRB137) after 30 min, 1 hour, 2 hours, 4 hours and 6 hours stimulation. Figure 30D depicts representative luciferase reporter assay results demonstrating the time kinetics of NF-^B activation (represented by fold induction of luminescence signal normalized to unstimulated control) in A549 NF-^B-luc reporter cells cultured in huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated plates, by EDB-bivalent × LT^R-bivalent antibody (LTBRB146), EDB- bivalent × LT^R-monovalent antibody (LTBRB384), ^-EDB bivalent × LIGHT fusion protein (LTBRB162) and ^-EDB-bivalent x LT^1^2 fusion protein (LTBRB137) after 30 min, 1 hour, 2 hours, 4 hours and 6 hours stimulation. Figure 30E depicts representative luciferase reporter assay results demonstrating NF-kB activation in A549 NF-kB-luc reporter cells cultured in huFn-7-EDB- 8-9 (EDB+, 3µg / mL)-precoated plates, as a fold induction in luminescence signal normalized to unstimulated control, by a-EDB-bivalent x LIGHT fusion protein (LTBRB162) and EDB-bivalent × LTbR-monovalent (LTBRB384) and EDB-bivalent × LTbR-bivalent (LTBRB146) antibodies. On the left, representative experimental results demonstrating NF-kB signaling induction in A549 NF-kB-luc reporter cells cultured for 16-20 hours by EDB × LTbR antibodies (LTBRB146 and LTBRB384) and their respective controls (a-RSV x LTbR, LTBRB381 and LTBRB387, respectively) are shown. On the right, representative experimental results comparing NF-kB signaling induction with EDB x LTbR antibody (LTBRB146) and a-EDB x LIGHT fusion protein (LTBRB162), and their respective controls (a-RSV x LTbR, LTBRB387 and a-RSV x LIGHT, LTBRB162) in A549 NF-kB-luc reporter cells cultured for 16-20 hours are shown.093699.0207 PATENT Figure 31 depicts representative results of cytokine release induction (IL-6, left; IP-10, middle and ITAC, right) in WI-38-132RA co-cultured with A375 for 24 hours by EDB × LTbR antibodies (LTBRB146 and LTBRB384) and their respective controls (a-RSV × LTbR, LTBRB381 and LTBRB387), and a-EDB × LIGHT fusion protein (LTBRB162) and its control (a-RSV × LIGHT, LTBRB29). Figures 32A-32D show the effects of LTBR146 on monocyte migration. Figure 32A shows a schematic of the endothelial cell layer transmigration assay. Figure 32B shows cell surface expression of LTBR on HUVEC cells. Figure 32C depicts a representative time course profile of monocyte transmigration under flow through a monolayer of pre-activated human umbilical vein endothelial cell (HUVEC) cultured on huFn-7-EDB-8-9 (EDB+, 3µg / mL)-precoated microscope flow chamber slide. HUVEC cells were pre-activated for 1 day with EDB-bivalent × LT^R antibodies, a-EDB × LIGHT fusion protein (filled symbols, LTBRB146, LTBRB384, and LTBRB162) or control ^-RSV × LT^R antibodies or a-RSV × LIGHT fusion protein (LTBRB387, LTBRB381, and LTBRB29, respectively). Monocytes were flowed over activated HUVECs for 6 minutes, followed by a 50-minute co-culture step with wash buffer, where monocytes were individually tracked and their positions marked at 1-minute intervals. Transmigration events were captured and counted per unit field. All experiments were carried out using triplicate fields and presented as a mean value with + standard error measurements (+SEM). Figure 32D depicts representative results of a monocyte transmigration flow assay demonstrating individual EC50 profiles for EDB-bivalent × LT^R antibodies, ^-EDB × LIGHT fusion protein (filled symbols, LTBRB146, LTBRB384, and LTBRB162) or control ^-RSV × LTbR antibodies or ^-RSV × LIGHT fusion protein (LTBRB387, LTBRB381, and LTBRB29, respectively) using AUC summary values of monocyte capture and transmigration. Profiles and non-linear fit were calculated using GraphPad Prism 9.0 (Function: [Agonist] vs. response – variable slope). DETAILED DESCRIPTION OF THE INVENTION Various publications, articles and patents are cited or described in the background and throughout the specification; each of these references is herein incorporated by reference in its entirety. Discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is for the purpose of providing context for the invention. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any inventions disclosed or claimed.093699.0207 PATENT Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention pertains. Otherwise, certain terms used herein have the meanings as set forth in the specification. It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Unless otherwise stated, any numerical values, such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.” Thus, a numerical value typically includes ± 10% of the recited value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Likewise, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). As used herein, the use of a numerical range expressly includes all possible subranges, all individual numerical values within that range, including integers within such ranges and fractions of the values unless the context clearly indicates otherwise. Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents are intended to be encompassedby the invention. As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains” or “containing,” or any other variation thereof, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers and are intended to be non-exclusive or open-ended. For example, a composition, a mixture, a process, a method, an article, or an apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). As used herein, the conjunctive term “and / or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and / or,” a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one093699.0207 PATENT of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and / or” as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term “and / or.” As used herein, the term “consists of,” or variations such as “consist of” or “consisting of,” as used throughout the specification and claims, indicate the inclusion of any recited integer or group of integers, but that no additional integer or group of integers can be added to the specified method, structure, or composition. As used herein, the term “consists essentially of,” or variations such as “consist essentially of” or “consisting essentially of,” as used throughout the specification and claims, indicate the inclusion of any recited integer or group of integers, and the optional inclusion of any recited integer or group of integers that do not materially change the basic or novel properties of the specified method, structure or composition. See M.P.E.P. § 2111.03. As used herein, “subject” means any animal, preferably a mammal, most preferably ahuman. The term “mammal” as used herein, encompasses any mammal. Examples of mammalsinclude, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guineapigs, monkeys, humans, etc., preferably a human. It should also be understood that the terms “about,” “approximately,” “generally,” “substantially,” and like terms, used herein when referring to a dimension or characteristic of a component of the preferred invention, indicate that the described dimension / characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one having ordinary skill in the art. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences (e.g., anti-LTΒR bispecific antibodies and polynucleotides that encode them, anti-LTΒR / anti-EDB bispecific antibodies and polynucleotides that encode them, LTβR polypeptides and LTβR polynucleotides that encode them, EDB polypeptides and EDB polynucleotides that encode them), refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection. For sequence comparison, typically one sequence acts as a reference sequence, to whichtest sequences are compared. When using a sequence comparison algorithm, test and reference093699.0207 PATENT sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see generally, Current Protocols in Molecular Biology, F.M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 Supplement) (Ausubel)). Examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol.215: 403-410 and Altschul et al. (1997) Nucleic Acids Res.25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al, supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity × from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and × determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W)093699.0207 PATENT of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)). In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001. A further indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions. As used herein, the term “polynucleotide,” synonymously referred to as “nucleic acid molecule,” “nucleotides” or “nucleic acids,” refers to any polyribonucleotide or polydeoxyribonucleotide, which can be unmodified RNA or DNA or modified RNA or DNA. “Polynucleotides” include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that can be single-stranded or, more typically, double-stranded or a mixture of single- and double- stranded regions. In addition, “polynucleotide” refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. “Polynucleotide” also embraces relatively short nucleic acid chains, often referred to as oligonucleotides. As used herein, the term “vector” is a replicon in which another nucleic acid segment can be operably inserted so as to bring about the replication or expression of the segment.093699.0207 PATENT As used herein, the term “host cell” refers to a cell comprising a nucleic acid molecule of the invention. The “host cell” can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. In one embodiment, a “host cell” is a cell transfected with a nucleic acid molecule of the invention. In another embodiment, a “host cell” is a progeny or potential progeny of such a transfected cell. A progeny of a cell may or may not be identical to the parent cell, e.g., due to mutations or environmental influences that can occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome. The term “expression” as used herein, refers to the biosynthesis of a gene product. The term encompasses the transcription of a gene into RNA. The term also encompasses translation of RNA into one or more polypeptides, and further encompasses all naturally occurring post-transcriptional and post-translational modifications. The expressed multispecific binding molecule, e.g. bispecific antibody, can be within the cytoplasm of a host cell, into the extracellular milieu such as the growth medium of a cell culture or anchored to the cell membrane. Preferably the multispecific binding molecule is secreted from production host cells into the culture medium. As used herein, the terms “peptide,” “polypeptide,” or “protein” can refer to a molecule comprised of amino acids and can be recognized as a protein by those of skill in the art. The conventional one-letter or three-letter code for amino acid residues is used herein. The terms “peptide,” “polypeptide,” and “protein” can be used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. The peptide sequences described herein are written according to the usual convention whereby the N-terminal region of the peptide is on the left and the C-terminal region is on the right. Although isomeric forms of the amino acids are known, it is the L-form of the amino acid that is represented unless otherwise expressly indicated. A “multispecific binding molecule” as used herein means a molecule that specifically binds to at least two different molecules (e.g., a bispecific binding molecule binds two different molecules, a trispecific binding molecule binds three different molecules). Preferably, the molecule is a protein, for instance comprising an antibody or fragment or derivative thereof. A multispecific binding molecule or antibody of the invention has at least one binding domain specifically binding093699.0207 PATENT to LTΒR, and at least one binding domain specifically binding to a tumor-associated antigen, and in view of the presence of a binding specificity towards LTβR is sometimes referred to as “anti- LTΒR” binding molecule or antibody herein. As used herein, the term “valent” refers to the presence of a specified number of binding sites in an antigen-binding molecule. A natural antibody for example, or a full-length antibody, has two binding sites and is bivalent. As such, the terms “monovalent,” “trivalent,” “tetravalent,” “pentavalent,” and “hexavalent” denote the presence of one binding site, three binding sites, four binding sites, five binding sites, and six binding sites, respectively, in an antibody. Specificity and valency are independent of each other and should not be read as interchangeable. For example, a monospecific antibody will bind one specific molecule, however the antibody may have one binding site, two binding sites, three binding sites, four binding sites, five binding sites, six binding sites, or more binding sites for that specific molecule, i.e., a monospecific monovalent antibody, a monospecific bivalent antibody, a monospecific trivalent antibody, etc. Similarly, a bispecific antibody may have the same or different valency for both antigens the bispecific antibody binds to. For example, a bispecific antibody that binds EDB and LTβR (EDB × LTβR) may be bivalent (e.g., EDB-monovalent × LTβR-monovalent), trivalent (EDB-monovalent × LTβR-bivalent; EDB- bivalent × LTβR-monovalent), tetravalent (EDB-monovalent × LTβR-trivalent; EDB-bivalent × LTβR-bivalent; EDB-trivalent × LTβR-monovalent), pentavalent (EDB-monovalent × LTβR- tetravalent; EDB-bivalent × LTβR-trivalent; EDB-trivalent × LTβR-bivalent; EDB-tetravalent × LTβR-monovalent), etc. A “binding domain” as used herein means a functional part of a binding molecule, e.g. from an antibody, that confers specific binding of the binding molecule to a target molecule. Examples of binding domains are variable regions of antibodies that confer specific binding to a target molecule, and may be formed by more than one chain of an antibody, e.g. the variable domain of a heavy chain paired to the variable domain of a light chain, or by a single chain such as in scFv molecules, or e.g. a single domain such as VHH from llamas, e.g. nanobodies, etc. The target molecule of the present invention is LTβR or a tumor-associated antigen. The term “specific binding” as used herein refers to antibody binding to a predetermined antigen with greater affinity than for other antigens. Typically, the antibody binds to a predetermined antigen with a dissociation constant (KD) of about 1 × 10-7M or less, for example about 1 × 10-8M or less, about 1 × 10-9M or less, about 1 × 10-10M or less, about 1 × 10-11M or less, about 1 × 10-12M or less, about 1 × 10-13M or less or about 1 × 10-14M or less, typically with a KDthat is at least tenfold less than its KDfor binding to a non-specific antigen or epitope (e.g., BSA, casein). The dissociation constant can be measured using standard procedures. Antibodies093699.0207 PATENT that specifically bind to a predetermined antigen may, however, have cross-reactivity to other related antigens, for example to the same predetermined antigen from other species (homologs), such as human or monkey, for example Macaca fascicularis (cynomolgus, cyno) or Pan troglodytes (chimpanzee, chimp). The term “tumor associated antigen” or “TAA” as used herein means antigens present on tumor cells or present in the extracellular matrix of tumors, which antigens are not qualitatively different form antigens found on normal cells or in extracellular matrix of normal tissues, but which are quantitatively different in some respect, e.g. they are present on tumor cells or in the extracellular matrix of tumors in significantly greater amounts, in higher density, at a different site of expression, and / or are differentially accessible to the immune system, etc. In certain embodiments, the tumor associated antigen is present on tumor cells or in the tumor extracellular matrix in an at least two times higher amount as on non-tumor cells or extracellular matrix, more preferably an at least five times higher amount, such as e.g. an at least 10-times higher amount, even more preferably an at least 100-times higher amount, such as e.g. an at least 1000-times higher amount and most preferably an at least 10,000-times higher amount. EDB is present in fibronectin in the extracellular matrix of tumor tissue, whereas it is typically not detectable in fibronectin forms that are present in normal tissue (i.e. the same tissue under normal conditions and not being in a tumor environment). The term “extracellular matrix” as used herein means a non-cellular component present within all tissues and organs in the form of a three-dimensional network of extracellular macromolecules, such as collagen, enzymes, and glycoproteins, that provide structural and biochemical support of surrounding cells. Its exact composition varies for different tissues, but it is generally made up of proteoglycans, water, minerals, and fibrous proteins. A proteoglycan is composed of a protein core surrounded by long chains of starch-like molecules called glycosaminoglycans. Two main classes of extracellular matrix molecules make up the matrix: proteoglycans, and fibrous proteins, including for example collagen, elastin, fibronectin, and laminin. Antibodies The invention generally relates to anti-LTΒR multispecific binding molecules, nucleic acids and expression vectors encoding the multispecific binding molecules, recombinant cells containing the vectors, and compositions comprising the multispecific binding molecules. In preferred embodiments, the anti-LTΒR multispecific binding molecules are anti-LTΒR multispecific antibodies, such as anti-LTΒR bispecific antibodies or antigen binding fragments093699.0207 PATENT thereof. In certain embodiments, the anti-LTΒR multispecific binding molecules can comprise binding domains specifically binding to LTβR which binding domains are in a different format than antibodies or functional fragments thereof, e.g. they may comprise anti-LTΒR Fynomers, anti- LTΒR affimers, anti-LTΒR darpins, and / or other protein scaffolds screened for candidates that specifically bind to LTΒR. In multispecific binding molecules of the invention, the binding domain with specificity towards LTβR is not provided by LIGHT or LTα1β2 (natural ligands of LTΒR), nor functional fragments or derivatives thereof such as 3xhmLIGHT. In preferred embodiments a binding domain with specificity towards LTβR in the multispecific binding molecules of the invention comprise an antibody against LTΒR, preferably an agonistic antibody against LTΒR, or a functional fragment or derivative thereof, such as an scFv. Agonistic antibodies against LTβR as such have been described, and non-limiting examples are BHA10 (e.g. WO2004002431), and CBE11 (e.g. WO0230986), or can alternatively be generated according to known methods for antibody generation, such as immunization of mice, phage display, etc. Fyn SH3-derived polypeptides or ‘Fynomers’ are well known in the art and have been described e.g. in Grabulovski et al. (2007) JBC, 282, p. 3196-3204; WO 2008 / 022759; Bertschinger et al (2007) Protein Eng Des Sel 20(2):57-68; and Gebauer and Skerra (2009) Curr Opinion in Chemical Biology 13:245-255. The term "Fyn SH3-derived polypeptide", used interchangeably herein with the term "Fynomer", refers to a non-immunoglobulin-derived binding polypeptide (e.g. a so-called scaffold as described in Gebauer and Skerra (2009) Curr Opinion in Chemical Biology 13:245-255) derived from the human Fyn SH3 domain. Fynomers are small, about 7-kDa, globular polypeptides. The SH3 domain of the human Fyn kinase was successfully used as a scaffold to engineer proteins (Fyn SH3-derived binding proteins termed Fynomers) that bind with high affinity and specificity to different target proteins (WO 2008 / 022759, WO 2011 / 023685, WO 2013 / 135588, WO 2014 / 170063, Grabulovski D. et al., (2007) J Biol Chem 282, p.3196-3204, Bertschinger J. et al. (2007) Protein Eng Des Sel, 20, p.57-68, and Schlatter et al. (2012) mAbs, 4(4) p.497-50). Affimer molecules are small proteins (12-14 kDa) that bind to target molecules with similar specificity and affinity to that of antibodies. These engineered non-antibody binding proteins are designed to mimic the molecular recognition characteristics of monoclonal antibodies in different applications (see e.g. Tiede et al, eLife 2017, DOI: 10.7554 / eLife.24903). DARPins (for designed ankyrin repeat proteins) are genetically engineered antibody mimetic proteins, typically exhibiting highly specific protein binding, and are derived from natural ankyrin proteins. They consist of at least three repeat motifs, and typically their molecular mass is093699.0207 PATENT about 14 or 18 kDa for four- or five-repeat DARPins, respectively. DARPin designs were for instance described in Binz et al, 2003, J. Mol. Biol.332: 489-503. Other binding protein formats, such as protein scaffolds, are known in the art and can also be used to provide one or more binding domains of certain embodiments of multispecific binding molecules of the invention. In preferred embodiments of the invention, the binding domain that binds to LTβR activates LTβR upon binding and is derived from an antibody, preferably an agonistic antibody, that specifically binds to LTΒR. In specific embodiments, the binding domain that binds to LTβR is a single chain variable domain (scFv) of an antibody, which scFv can be in any available format, e.g. stabilized by methods described previously and / or herein. The invention in certain embodiments relates to anti-LTΒR / anti-TAA multispecific antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the multispecific antibodies. In certain embodiments, the anti-LTΒR / anti-TAA multispecific antibody or antigen-binding fragment is an anti-LTΒR / anti-EDB multispecific antibody or antigen-binding fragment. Methods of making the multispecific binding molecules and / or antibodies, and methods of using the multispecific binding molecules and / or antibodies to treat diseases, including cancer, are also provided. The multispecific binding molecules and / or antibodies disclosed herein possess one or more desirable functional properties, including but not limited to one or more of specific binding to LTβR and a TAA, high specificity to LTβR and a TAA, and / or the ability to treat or prevent cancer when administered alone or in combination with other anti-cancer therapies. As used herein, the term “antibody” is used in a broad sense and includes immunoglobulin or antibody molecules including human, humanized, composite and chimeric antibodies and antigen binding domains that are monoclonal or polyclonal. In general, antibodies are proteins or peptide chains that exhibit binding specificity to a specific antigen. Antibody structures are well known. Immunoglobulins can be assigned to five major classes (i.e., IgA, IgD, IgE, IgG and IgM), depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub- classified as the isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Accordingly, the antibodies of the invention can be of any of the five major classes or corresponding sub-classes. Preferably, the antibodies of the invention are IgG1, IgG2, IgG3 or IgG4. Antibody light chains of vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequences of their constant domains. Accordingly, the antibodies of the invention can contain a kappa or lambda light chain constant domain. According to particular embodiments, the antibodies of the invention include heavy and / or light chain constant regions from rat or human093699.0207 PATENT antibodies. In addition to the heavy and light constant domains, antibodies contain an antigen- binding region that is made up of a light chain variable region and a heavy chain variable region, each of which contains three domains (i.e., complementarity determining regions 1-3; CDR1, CDR2, and CDR3). The light chain variable region domains are alternatively referred to as LCDR1, LCDR2, and LCDR3, and the heavy chain variable region domains are alternatively referred to as HCDR1, HCDR2, and HCDR3. As used herein, the terms “variable region” and “variable domain” refer to the portions of the light and heavy chains of an antibody that include amino acid sequences of complementary determining regions (CDRs, e.g., CDR L1, CDR L2, CDR L3, CDR H1, CDR H2, and CDR H3) and framework regions (FRs). According to the methods used in this disclosure, the amino acid positions assigned to CDRs and FRs are defined according to Kabat (Sequences of Proteins of Immunological Interest, 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a CDR (defined further herein) or FR (defined further herein) of the variable region. For example, a heavy chain variable region may include a single inserted residue (i.e., residue 52a according to Kabat) after residue 52 of CDR H2 and inserted residues (i.e., residues 82a, 82b, 82c, etc. according to Kabat) after residue 82 of heavy chain FR. The Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence. “Complementarity determining regions” (CDR) are antibody regions that bind an antigen. There are three CDRs in the VH (HCDR1, HCDR2, HCDR3) and three CDRs in the VL (LCDR1, LCDR2, LCDR3). CDRs may be defined using various delineations such as Kabat (Wu et al. (1970) J Exp Med 132: 211-50; Kabat et al., Sequences of Proteins of Immunological Interest, 5thEd. Public Health Service, National Institutes of Health, Bethesda, Md., 1991), Chothia (Chothia et al. (1987) J Mol Biol 196: 901-17), IMGT (Lefranc et al. (2003) Dev Comp Immunol 27: 55- 77) and AbM (Martin and Thornton J Bmol Biol 263: 800-15, 1996). The correspondence between the various delineations and variable region numbering is described (see e.g., Lefranc et al. (2003) Dev Comp Immunol 27: 55-77; Honegger and Pluckthun, J Mol Biol (2001) 309:657-70; International ImMunoGeneTics (IMGT) database; Web resou: / / www_imgt_org). Available programs such as abYsis by UCL Business PLC may be used to delineate CDRs. The term “CDR”, “HCDR1”, “HCDR2”, “HCDR3”, “LCDR1”, “LCDR2” and “LCDR3” as used herein includes CDRs defined by any of the methods described supra, Kabat, Chothia, IMGT or AbM, unless otherwise explicitly stated in the specification.093699.0207 PATENT As used herein, the term an “isolated antibody” refers to an antibody which is substantially free of other antibodies having different antigenic specificities (e.g., an isolated bispecific antibody that specifically binds to LTβR is substantially free of bispecific antibodies that do not bind to LTβR; e.g., an isolated bispecific antibody that specifically binds to LTβR and / or EDB is substantially free of bispecific antibodies that do not bind to LTβR and / or EDB). In addition, an isolated antibody is substantially free of other cellular material and / or chemicals. As used herein, the term “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that can be present in minor amounts. The monoclonal antibodies of the invention can be made by the hybridoma method, phage display technology, single lymphocyte gene cloning technology, or by recombinant DNA methods. For example, the monoclonal antibodies can be produced by a hybridoma which includes a B cell obtained from a transgenic nonhuman animal, such as a transgenic mouse or rat, having a genome comprising a human heavy chain transgene and a light chain transgene. In certain embodiments, monoclonal antibodies are produced by a recombinant host cell that expresses nucleic acid sequences encoding the antibody. Such a recombinant host cell can for instance be obtained by transfection of the nucleic acid sequences into a parent cell, e.g. a CHO cell. The recombinant host cell can be cultured under conditions conducive to expression of the antibody in the host cell, and the antibody can be isolated from the host cell, the culture medium, or both. In certain embodiments, a multispecific binding molecule of the invention comprises an antibody or one or more antigen-binding fragments thereof. As used herein, the term “antigen- binding fragment” refers to an antibody fragment such as, for example, a diabody, a Fab, a Fab', a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), a single domain antibody (sdab) an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not comprise a complete antibody structure. An antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment binds. According to particular embodiments, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain. According to other particular embodiments, the antigen-binding fragment comprises Fab and F(ab’). “Fab” or “Fab fragment” refers to an antibody fragment composed of VH, CH1, VL and CL domains. In some embodiments, the antigen binding fragments include IgG-like093699.0207 PATENT molecules with complementary CH3 domains to force heterodimerization; recombinant IgG-like dual targeting molecules, wherein the two sides of the molecule each contain the Fab fragment or part of the Fab fragment of at least two different antibodies; IgG fusion molecules, wherein full length IgG antibodies are fused to an extra Fab fragment or parts of Fab fragment; Fc fusion molecules, wherein single chain Fv molecules or stabilized diabodies are fused to heavy-chain constant-domains, Fc-regions or parts thereof; Fab fusion molecules, wherein different Fab- fragments are fused together; ScFv- and diabody-based and heavy chain antibodies (e.g., domain antibodies, nanobodies) wherein different single chain Fv molecules or different diabodies or different heavy-chain antibodies (e.g. domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule. In some embodiments, IgG-like molecules with complementary CH3 domains molecules include the Triomab / Quadroma (Trion Pharma / Fresenius Biotech), the Knobs-in-Holes (Genentech), CrossMAbs (Roche) and the electrostatically-matched (Amgen), the LUZ-Y (Genentech), the Strand Exchange Engineered Domain body (SEEDbody)(EMD Serono), the Biclonic (Merus) or the DuoBody (Genmab A / S, see e.g. Labrijn et al, 2013, PNAS 110: 5145-5150). In some embodiments, the antigen binding fragments include “Stapled single chain Fv” or “spFv” refers to a scFv that comprises one or more disulfide bonds between the VH and the linker or the VL and the linker. Typically the spFv may comprise one disulfide bond between the VH and the linker, one disulfide bond between the VL and the linker, or two disulfide bonds between the VH and the linker and the VL and the linker. scFv molecules which comprise disulfide bonds between the VH and the VL are excluded from the term “spFv”. As used herein, the term “single-chain antibody” refers to a conventional single-chain antibody in the field, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide, e.g. of about 15 to about 20 amino acids. As used herein, the term “single domain antibody” refers to a conventional single domain antibody in the field, which comprises a heavy chain variable region and a heavy chain constant region or which comprises only a heavy chain variable region. In certain embodiments, multispecific binding molecules of the invention comprise an antibody with one or more mutations in the Fc that abrogate binding to protein A. Such mutations facilitate purification of heterodimer, and have for instance been described in WO2010151792. As used herein, the term “human antibody” refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, antigen-binding fragments thereof, and / or antibodies comprising at least one human heavy and / or light chain polypeptide.093699.0207 PATENT As used herein, the term “humanized antibody” refers to a non-human antibody that is modified to increase the sequence homology to that of a human antibody, such that the antigen- binding properties of the antibody are retained, but its antigenicity in the human body is reduced. As used herein, the term “chimeric antibody” refers to an antibody wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species. The variable region of both the light and heavy chains often correspond to the variable region of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capability, while the constant regions correspond to the sequences of an antibody derived from another species of mammal (e.g., human) to avoid eliciting an immune response in that species. As used herein, the term “multispecific antibody” refers to an antibody that comprises a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In an embodiment, the first and second epitopes do not overlap or do not substantially overlap. In an embodiment, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a multimeric protein). In certain embodiments, a multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain, or even more immunoglobulin variable domains. In an embodiment, a multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule. As used herein, the term “bispecific antibody” refers to a multispecific antibody that binds no more than two epitopes, preferably no more than two antigens. A bispecific antibody is characterized by a first immunoglobulin variable domain which has binding specificity for a first epitope (e.g., an epitope on a LTβR antigen) and a second immunoglobulin variable domain that has binding specificity for a second epitope (e.g., an epitope on a tumor-associated antigen (TAA),). In an embodiment, a bispecific antibody comprises a first heavy chain variable domain and a first light chain variable domain which form a binding domain having binding specificity for a first epitope and a second heavy chain variable domain and a second light chain variable domain which form a binding domain having binding specificity for a second epitope. In an embodiment, a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope. In an embodiment, a bispecific antibody comprises a scFv, or fragment thereof, having binding specificity for a first epitope, and a scFv, or fragment thereof, having binding specificity for a second epitope. In an embodiment, a bispecific antibody comprises a scFv, or fragment093699.0207 PATENT thereof, having binding specificity for a first epitope, and a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a second epitope. In preferred embodiments of the invention, the first epitope is located on LTβR and the second epitope is located on a tumor-associated antigen (TAA), e.g., fibronectin, in particular EDB thereof. In certain embodiments, a multispecific binding molecule according to the invention comprises an antibody, e.g. an IgG, with an scFv fused to the antibody. The scFv may in certain embodiments have binding specificity for LTβR. Both arms (comprising the variable regions) of the antibody may in certain embodiments bind to a TAA (e.g., EDB of fibronectin). The scFv may be fused to a light chain of the antibody or to a heavy chain of the antibody, and may be fused to the N-terminus or to the C-terminus of the heavy or light chain. In certain embodiments, the scFv is fused to the N-terminus of the heavy chain. In other embodiments, the scFv is fused to the C- terminus of the heavy chain. It will be clear to the skilled person based on the instant disclosure that other forms are also possible, e.g., wherein a bispecific antibody comprising one arm specifically binding to LTβR and another arm specifically binding to a TAA is supplemented by fusing an scFv specifically binding to TAA to one of the chains of the antibody, etc. “Epitope" refers to a portion of an antigen to which an antibody specifically binds. Epitopes typically consist of chemically active (such as polar, non-polar or hydrophobic) surface groupings of moieties such as amino acids or polysaccharide side chains and may have specific three- dimensional structural characteristics, as well as specific charge characteristics. An epitope may be composed of contiguous and / or discontiguous amino acids that form a conformational spatial unit. For a discontiguous epitope, amino acids from differing portions of the linear sequence of the antigen come in close proximity in 3-dimensional space through the folding of the protein molecule. Antibody “epitope” depends on the methodology used to identify the epitope. As used herein, the term “ LTΒR” refers to a polypeptide that is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release, which is a member of the tumor necrosis factor receptor superfamily. LTβR can also be referred to as “tumor necrosis factor receptor superfamily member 3 (TNFRSF3).” LTβR is expressed on the surface of many cell types, including cells of epithelial and myeloid lineages. LTβR can specifically bind the lymphotoxin membrane form (a complex of lymphotoxin-alpha and lymphotoxin-beta). Activation of LTβR can trigger apoptosis via TRAF3 and TRAF5 and can lead to the release of interleukin 8. Unless noted, preferably the LTβR is a human LTβR. A human LTβR amino acid sequence is provided by UniProt number P36941.093699.0207 PATENT The term “TAA” or “tumor-associated antigen” refers to a protein or glycoprotein that is relatively restricted to tumor cells, including tumor-specific antigens (TSAs), capable of inducing an immune response. The term “EDB” or “extra domain B” refers to a domain of fibronectin that can be included in fibronectin molecules based on the splicing pattern of the fibronectin pre-mRNA. Extra domain B is a complete fibronectin (FN) type III repeat that comprises 91 amino acid residues. Generally, EDB is undetectable in normal adult tissues, but exhibits greater expression in fetal and tumor tissues in the extracellular matrix, and accumulates around neovasculature during angiogenic processes, thus making EDB a potential marker and target of angiogenesis. Unless noted, preferably EDB is a human EDB. A human EDB containing fibronectin isoform amino acid sequence is provided by UniProt number P02751. The term “fibronectin” refers to a polypeptide that is a high molecular weight glycoprotein of the extracellular matrix. Fibronectin can bind to membrane-spanning receptor proteins, referred to as integrins. Fibronectin can also bind other extracellular matrix proteins, such as collagen, fibrin, and heparan sulfate proteoglycans. Fibronectin can exist as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds. Fibronectin is produced from a single gene, but alternative splicing of the fibronectin pre-mRNA molecule leads to the creation of several isoforms of fibronectin, one of which is EDB fibronectin. Fibronectin can play a role in cell adhesion, growth, migration, and differentiation, and it can be important for processes such as wound healing and embryonic development. A human fibronectin amino acid sequence is provided by UniProt number P02751, which contains extra domain B, and NCBI Accession Numbers NP_001263337 (isoform (b), NP_001263338 (isoform (c), NP_001263339 (isoform (d), NP_001263340 (isoform (e), and NP_001263341 (isoform f), NP_001293058 (isoform 8), NP_001293059 (isoform 9), NP_001293060 (isoform 10), NP_001293061 (isoform 11), and NP_002017 (isoform 3). The terms "prostate specific membrane antigen" and "PSMA" are used interchangeably herein, and include any variants, isoforms and species homologs of human PSMA that are naturally expressed by cells. The complete amino acid sequence of human PSMA protein has the GenBank accession number NP_004467. The term “mesothelin,” as used herein, refers to any native, mature mesothelin which results from processing of a mesothelin precursor protein in a cell. The term includes mesothelin from any vertebrate source, including mammals such as primates (e.g. humans and cynomolgus monkeys) and rodents (e.g., mice and rats), unless otherwise indicated. The term also includes naturally occurring variants of mesothelin, e.g., splice variants or allelic variants. The093699.0207 PATENT amino acid sequence of an exemplary human mesothelin precursor protein is shown in GenBank accession number NP_005814. “EGFR” or “Epidermal growth factor receptor” as used here refers to the human EGFR (also known as HER1 or ErbB1 having the amino acid sequence shown in GenBank accession number NP_005219, as well as naturally-occurring variants thereof. Such variants include well-known EGFRvIII and other alternatively spliced variants (e.g., as identified by SwissProt Accession numbers P00533-1 (wild type; identical to NP_005219), P00533-2 (F404L / L4055), P00533-3 (628-705: CTGPGLEGCP . . . GEAPNQALLR [SEQ ID NO: 2472] →PGNESLKAML . . . SVIITASSCH [SEQ ID NO: 2473] and 706-1210 deleted), P00533-4 (C628S and 629-1210 deleted), variants GlnQ98, R266, K521, 1674, G962, and P988, T790M, L858R / T790M and del(E746, A750). As used herein, an antibody or binding molecule that “specifically binds to LTΒR” refers to an antibody or molecule comprising an antigen binding domain thereof that binds to a LTβR, preferably a human LTβR, with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. The term “KD” refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system, e.g., a BIACORE® system, or by using bio-layer interferometry technology, such as an Octet RED96 system. In preferred embodiments a binding domain with specificity towards LTβR in the multispecific binding molecules of the invention comprise an antibody against LTβR, preferably an agonistic antibody against LTβR, or a functional fragment or derivative thereof, such as an scFv. An “agonistic antibody against LTβR” as used herein is an antibody binding to LTβR and capable of inducing downstream signaling either directly or upon higher order clustering, e.g. by immobilization to a solid support, by use of cross-linking antibodies, etc. Agonistic antibodies against LTβR as such have been described, and non-limiting examples are BHA10 (e.g. WO2004002431), CBE11 (e.g. WO0230986), REA412 (commercially available from Miltenyi Biotec), 31G4D8 (commercially available from BioLegend), and 71319 / MAB629 (commercially available from Novus Biologicals), or can alternatively be generated according to known methods for antibody generation, such as immunization of mice, phage display, etc. The smaller the value of the KD of an antibody, the higher affinity that the antibody binds to a target antigen.093699.0207 PATENT In one aspect, provided herein is a binding agent comprising an antigen binding region that binds LTβR (e.g., human LTβR). In some embodiments, the present binding agent comprises at least one portion that is a polypeptide. In some embodiments, the present binding agent comprises at least one portion that is not a polypeptide. In some embodiments, the present binding agents are LTβR binding proteins. In some embodiments, the present disclosure provides binding agents (e.g., antibodies or proteins) that bind LTβR. In some embodiments, the LTβR binding agent binds an LTβR protein or a fragment thereof of a mammalian origin. In some embodiments, the LTβR binding agent binds a human LTβR protein or a fragment thereof. In some embodiments, the LTβR binding agent binds a LTβR protein or a fragment thereof originated from a non-human mammalian species. In some embodiments, the non-human mammalian species is a rodent (e.g., mice and rats). In some embodiments, the non-human mammalian species is a dog. In some embodiments, the non-human mammalian species is a cynomolgus monkeys (cynomolgus). In some embodiments, the binding agent comprises an antigen binding region that binds to LTβR. In some embodiments, the LTβR binding region in the present binding protein is an antibody or a binding domain derived from an antibody. In some embodiments, the antibody is a recombinant antibody. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the antibody is an IgG1 antibody. In some embodiments, the antibody is an IgG2 antibody. In some embodiments, the antibody is an IgG3 antibody. In some embodiments, the antibody is an IgG4 antibody. In some embodiments, the antibody comprises an IgG heavy chain. In some embodiments, the antibody comprises an IgG1 heavy chain. In some embodiments, the antibody comprises an IgG2 heavy chain. In some embodiments, the antibody comprises an IgG4 heavy chain. In some embodiments, the antibody comprises a kappa light chain. In some embodiments, the antibody comprises a kappa light chain constant region. In some embodiments, the antibody comprises a lambda light chain. In some embodiments, the antibody comprises a lambda light chain constant region. In some embodiments, the antibody is an antibody fragment comprising an antigen-binding site. In some embodiments, the antibody is an scFv. In some embodiments, the antibody is a disulfide-linked scFv. In some embodiments, the antibody is an spFv. In some embodiments, the antibody is a disulfide-linked sc(Fv)2. In some embodiments, the antibody is a Fab, Fab’, or a F(ab)2 antibody. In some embodiments, the antibody is a diabody. In some embodiments, the antibody is a nanobody. In some embodiments, the antibody is a monospecific antibody. In some embodiments,093699.0207 PATENT the antibody is a bispecific antibody. In some embodiments, the antibody is a trispecific antibody. In some embodiments, the antibody is a multispecific antibody. In some embodiments, the antibody is a monovalent antibody. In some embodiments, the antibody is a multivalent antibody. In some embodiments, the antibody is a bivalent antibody. In some embodiments, the antibody is a trivalent antibody. In some embodiments, the antibody is a tetravalent antibody. In some embodiments, the LTβR binding region provided herein binds to LTβR (e.g., human LTβR) with a dissociation constant (KD) of ≤ 1 μM, ≤ 100 nM, ≤ 10 nM, ≤ 1 nM, ≤ 0.1 nM, ≤ 0.01 nM, or ≤ 0.001 nM (e.g., 10-8 M or less, e.g., from 10-8 M to 10-13 M, e.g., from 10- 9 M to 10-13 M). In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 0.01 nM. In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 0.1 nM. In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 0.5 nM. In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 1.0 nM. In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 1.5 nM. In some embodiments, the LTβR binding region provided herein binds to LTβR with a dissociation constant of ≤ 3.0 nM. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present disclosure, including by RIA, for example, performed with the Fab version of an antibody of interest and its antigen (Chen et al., 1999, J. Mol Biol 293:865-81); by biolayer interferometry (BLI) or surface plasmon resonance (SPR) assays by Octet®, using, for example, an Octet®Red96 system, or by Biacore®, using, for example, a Biacore®TM-2000 or a Biacore®TM-3000. An “on-rate” or “rate of association” or “association rate” or “kon” may also be determined with the same biolayer interferometry (BLI) or surface plasmon resonance (SPR) techniques described above using, for example, the Octet®Red96, the Biacore®TM-3000, or the Biacore®TM-8000 system. In some embodiments, provided herein are isolated anti-lymphotoxin beta receptor (LTβR) monoclonal antibodies or antigen binding fragments thereof. In certain non-limiting embodiments, the binding domain that specifically binds to LTβR comprises an anti-LTΒR antibody or a fragment or derivative thereof, for instance a single chain antibody fragment (scFv), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said VH and VL comprise HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 set forth in Table 1 below.093699.0207 PATENT In some embodiments, provided herein are isolated anti-lymphotoxin beta receptor ( LTΒR) monoclonal antibodies or antigen binding fragments thereof. In certain non-limiting embodiments, the binding domain that specifically binds to LTβR comprises an anti-LTΒR antibody or a fragment or derivative thereof, for instance a single chain antibody fragment (scFv), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH and VL are set forth in Tables 2 and 3. In some embodiments, an anti-LTΒR antibody or fragment or derivative thereof comprises a linker region. In some embodiments, the linker connects a VH and a VL region. In some embodiments, the linker connects a VH to a constant region. In some embodiments, the linker comprises an amino acid sequence of any one of SEQ ID NO:2450-2454. In some embodiments, the linker comprises SEQ ID NO:2452. In some embodiments, an anti-LTΒR antibody or fragment or derivative thereof is a stapled single chain antibody fragment (spFv) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity or 100% identity to the amino acid sequence of any one of SEQ ID NO:2190, 2191, and 2204-2449. In some embodiments, the binding domain that specifically binds to LTβR comprises an anti-LTΒR antibody or a fragment or derivative thereof, for instance a single variable domain on a heavy chain (VHH) antibody, comprising a VHH region comprising a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, wherein said VHH comprises HCDR1, HCDR2, and HCDR3 set forth in Table 1. In some embodiments, provided herein are isolated anti-lymphotoxin beta receptor (LTΒR) multispecific antibodies or antigen binding fragments thereof. In certain non-limiting embodiments, the binding domain that specifically binds to LTβR comprises an agonistic anti- LTΒR antibody or a fragment or derivative thereof, for instance a single chain antibody fragment (scFv), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH and VL are set forth in Tables 2 and 3. In some embodiments, provided herein are isolated anti-lymphotoxin beta receptor ( LTΒR) multispecific antibodies or antigen binding fragments thereof. In certain non-limiting embodiments, the binding domain that specifically binds to LTβR comprises (spFv) comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity or 100% identity to the amino acid sequence of any one of SEQ ID NO:2190, 2191, and 2204-2449. In some embodiments, the binding domain that specifically binds to LTβR comprises an agonistic anti-LTΒR antibody or a fragment or derivative thereof, for instance a single variable093699.0207 PATENT domain on a heavy chain (VHH) antibody, comprising a VHH region comprising a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, wherein said VHH comprises set forth in Table 1. In some embodiments, the binding domain that specifically binds to LTβR comprises an agonistic anti-LTΒR antibody or a fragment or derivative thereof, for instance a single variable domain on a heavy chain (VHH) antibody, comprising a VHH region comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity or 100% identity to the amino acid sequence of any one of SEQ ID NO: 230-249. In certain non-limiting embodiments, the second binding domain specifically binds to a tumor-associated antigen (TAA). In preferred embodiments a binding domain with specificity towards a TAA in the multispecific binding molecules of the invention comprise an antibody against the TAA, or a functional fragment or derivative thereof, such as an scFv. Antibodies against TAAs, such as EDB have been described, and a non-limiting examples are L19 (e.g. WO9745544) and other antibodies binding to ED-B or to adjacent domains (e.g. Carnemolla et al. Int. J. Cancer: 68,397-405 (1996)), or can alternatively be generated according to known methods for antibody generation, such as immunization of mice, phage display, etc. According to a particular aspect of the invention, provided herein are multispecific binding molecules. The multispecific binding molecules comprise (i) a first binding domain that specifically binds to a lymphotoxin beta receptor (LTΒR), and (ii) a second binding domain that specifically binds to a TAA, wherein the multispecific binding molecule activates LTβR upon binding of the TAA. In certain embodiments, the multispecific binding molecule activates LTβR in a tumor specific manner. Activating LTβR in a tumor specific manner, as used herein, means that the upon simultaneous binding of the multispecific binding molecule to LTβR and the TAA, which are both present in the tumor microenvironment either on the surface of a cell or present in the extracellular matrix, LTβR is activated to trigger signaling via canonical and / or non-canonical NF-κB pathway. Activation of NF-κB pathways can lead to the establishment of a pro-inflammatory tumor microenvironment via secretion of pro-inflammatory chemokines and cytokines and expression of adhesion molecules on the surface of the cell. Simultaneous binding of the multispecific binding molecule results in activation of LTβR in the tumor. If the TAA is not present in normal tissue, i.e., normal cells, or not present in the extracellular matrix adjacent to normal tissue, the multispecific binding molecule can on normal tissue only bind LTΒR, which will not result in the activation of LTβR in normal tissue. This is a significant advantage over molecules described in the prior art that are based on natural LTβR ligands, e.g. LIGHT-antibody fusions, which can093699.0207 PATENT activate LTβR independent of a TAA, and thus are much less tumor specific for activation of LTβR as compared to the molecules of the invention, as shown in the examples herein. In certain embodiments, the multispecific binding molecule comprises two binding domains, such as for instance a bispecific antibody that comprises two antigen binding domains, one binding to LTβR and another one binding to TAA. In preferred embodiments, the multispecific binding molecule comprises more than two antigen binding domains, for instance one binding to LTβR and two binding to the TAA. In certain embodiments, the multispecific binding molecule comprises three binding domains. In certain embodiments, the three binding domains are all different and bind to three different antigens. In certain preferred embodiments, the three antigen binding domains comprise one binding domain that binds to a first antigen, and two binding domains that bind to a second antigen. In this embodiment, the three antigen binding domains are present in a 2:1 stoichiometry. The three antigen binding domains can, for example, comprise one first binding domain that specifically binds to an LTβR on an LTΒR-expressing cell. The three antigen binding domains can, for example, comprise two second binding domains that specifically bind TAA. In certain embodiments, the two second binding domains have identical binding specificity for the EGFR, e.g. the two second binding domains may be identical. It is shown herein that multispecific binding molecules of the invention that have more than one binding domain specific for EDB have further advantageous properties over multispecific binding molecules of the invention that have only one binding domain specific for EGFR. In certain embodiments, LTβR is activated upon binding of LTβR and the EGFR. In certain non-limiting embodiments, the second binding domain specifically binds to a tumor-associated antigen (TAA). In some embodiments, the second binding domain specifically binds to EDB, epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate-specific membrane antigen (PSMA), As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to a TAA” refers to an antigen binding domain or antigen binding fragment that binds a TAA (e.g., EDB, mesothelin (MSLN), etc.), with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to EDB” refers to an antigen binding domain or antigen binding fragment that binds EDB (e.g. in the form of EDB fibronectin), with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less.093699.0207 PATENT In certain non-limiting embodiments, the second binding domain that specifically binds to EDB comprises an antibody binding to EDB or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:702, 703, and 704, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:705, 706, and 707, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:6, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:7; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:252, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:253; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:475, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:476. As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to EGFR” refers to an antigen binding domain or antigen binding fragment that binds EGFR, with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. In certain non-limiting embodiments, the second binding domain that specifically binds to EGFR comprises an antibody binding to EGFR or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:708, 709, and 710, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:711, 712, and 713, respectively; or093699.0207 PATENT (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:8, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:9; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:254, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:255; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:477, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:478. As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to MSLN” refers to an antigen binding domain or antigen binding fragment that binds MSLN, with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. In certain non-limiting embodiments, the second binding domain that specifically binds to MSLN comprises an antibody binding to MSLN or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:714, 715, and 716, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:717, 718, and 719, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:10, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:11; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:256, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:257; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:481, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:482.093699.0207 PATENT As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to RSV” refers to an antigen binding domain or antigen binding fragment that binds RSV, with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. In certain non-limiting embodiments, the second binding domain that specifically binds to RSV comprises an antibody binding to RSV or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:725, 726, and 727, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:728, 729, and 730, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:14, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:15; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:260, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:261; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:483, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:484. As used herein, an antigen binding domain or antigen binding fragment that “specifically binds to gp120” refers to an antigen binding domain or antigen binding fragment that binds gp120, with a KD of 1 × 10−7M or less, preferably 1 × 10−8M or less, more preferably 5 × 10−9M or less, 1 × 10−9M or less, 5 × 10−10M or less, or 1 × 10−10M or less. In certain non-limiting embodiments, the second binding domain that specifically binds to gp120 comprises an antibody binding to gp120 or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region093699.0207 PATENT 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: (a) HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:731, 732, and 733, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:734, 735, and 736, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:16, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:17; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:262, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:263; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:479, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:480. In certain non-limiting embodiments, the multispecific binding molecule comprises: (i) a binding domain that specifically binds to LTβR or a fragment or derivative thereof, for instance a single chain antibody fragment (scFv) comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said LTΒR- binding domain comprises: (1) the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 set forth in Table 1; (2) the VH and VL set forth in Tables 2 and 3; or (3) an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NO:2190, 2191, and 2204-2449; and (ii) a second binding domain specifically binds to a tumor-associated antigen (TAA), wherein the second binding domain that comprises: (A) an antibody binding to EDB or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following:093699.0207 PATENT HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:702, 703, and 704, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:705, 706, and 707, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:6, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:7; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:252, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:253; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:475, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:476; (B) an antibody binding to EGFR or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:708, 709, and 710, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:711, 712, and 713, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:8, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:9; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:254, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:255; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:477, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:478; (C) an antibody binding to MSLN or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1093699.0207 PATENT (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:714, 715, and 716, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:717, 718, and 719, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:10, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:11; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:256, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:257; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:481, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:482; (D) an antibody binding to RSV or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:725, 726, and 727, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:728, 729, and 730, respectively; or a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:14, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:15; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:260, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:261; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:483, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:484; or093699.0207 PATENT (E) an antibody binding to gp120 or a fragment or derivative of such antibody, for instance comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3, and the VL comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3, wherein said antibody or fragment thereof comprise any of the following: HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:731, 732, and 733, respectively; and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:734, 735, and 736, respectively; or (a) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:16, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:17; (b) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:262, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:263; or (c) VH comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:479, and VL comprises an amino acid sequence having at least 90%, 95%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO:480. In some embodiments, provided herein are isolated anti-lymphotoxin beta receptor (LTΒR) multispecific antibodies or antigen binding fragments thereof, wherein the antibody comprises at least one heavy chain (HC1) and optionally a first light chain (LC1), a second heavy chain (HC2), and a second light chain (LC2), wherein the antibody comprises any heavy chains and / or light chains set forth in Table 4. In certain non-limiting embodiments, the multispecific binding molecule comprises any of the sequences set forth in Table 4. In some embodiments, the multispecific (e.g., bispecific) molecule induces NF-κB signaling in the presence of EDB that is at least 2-fold, such as at least 3-fold, for example at least 4-fold greater than the NF-κB signaling induced in the absence of EDB (under the same conditions). Sometimes the assay is an NF-κB luciferase reporter assay. The NF-κB luciferase reporter assay may be performed using the protocol of Example 9. In some embodiments, the heavy and light chains are humanized. In some embodiments, the heavy and light chains are human.093699.0207 PATENT In some embodiments, the bispecific antibodies include IgG-like molecules with complementary CH3 domains to force heterodimerization; recombinant IgG-like dual targeting molecules, wherein the two sides of the molecule each contain the Fab fragment or part of the Fab fragment of at least two different antibodies; IgG fusion molecules, wherein full length IgG antibodies are fused to an extra Fab fragment or parts of Fab fragment; Fc fusion molecules, wherein single chain Fv molecules or stabilized diabodies are fused to heavy-chain constant- domains, Fc-regions or parts thereof; Fab fusion molecules, wherein different Fab-fragments are fused together; ScFv- and diabody-based and heavy chain antibodies (e.g., domain antibodies, nanobodies) wherein different single chain Fv molecules or different diabodies or different heavy- chain antibodies (e.g. domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule. In some embodiments, IgG-like molecules with complementary CH3 domains molecules include the Triomab / Quadroma (Trion Pharma / Fresenius Biotech), the Knobs-into-Holes (Genentech), CrossMAbs (Roche) and the electrostatically-matched (Amgen), the LUZ-Y (Genentech), the Strand Exchange Engineered Domain body (SEEDbody) (EMD Serono), the Biclonic (Merus), or the DuoBody (Genmab A / S). In some embodiments, recombinant IgG-like dual targeting molecules include Dual Targeting (DT)-Ig (GSK / Domantis), Two-in-one Antibody (Genentech), Cross-linked Mabs (Karmanos Cancer Center), mAb2 (F-Star) or CovX-body (CovX / Pfizer). In some embodiments, IgG fusion molecules include Dual Variable Domain (DVD)-Ig (Abbott), IgG-like Bispecific (InnClone / Eli Lilly), Ts2Ab (MedImmune / AZ) and BsAb (Zymogenetics), HERCULES (Biogen Idec), or TvAb (Roche). In some embodiments, Fc fusion molecules can include ScFv / Fc Fusions (Academic Institution), SCORPION (Emergent BioSolutions / Trubion, Zymogenetics / BMS), Dual Affinity Retargeting Technology (Fc-DART) (MacroGenics), or Dual(ScFv)2-Fab (National Research Center for Antibody Medicine--China). In some embodiments, Fab fusion bispecific antibodies include F(ab)2 (Medarex / AMGEN), Dual-Action or Bis-Fab (Genentech), Dock-and-Lock (DNL) (ImmunoMedics), Bivalent Bispecific (Biotecnol), or Fab-Fv (UCB-Celltech). ScFv-, diabody- based, and domain antibodies, include but are not limited to, Bispecific T Cell Engager (BiTE) (Micromet), Tandem Diabody (Tandab) (Affimed), Dual Affinity Retargeting Technology (DART) (MacroGenics), Single-chain Diabody (Academic), TCR-like Antibodies (AIT, ReceptorLogics), Human Serum Albumin ScFv Fusion (Merrimack), or COMBODY (Epigen Biotech), dual targeting nanobodies (Ablynx), dual targeting heavy chain only domain antibodies.093699.0207 PATENT Full length bispecific antibodies of the invention can be generated for example using Fab arm exchange (or half molecule exchange) between two mono specific bivalent antibodies by introducing substitutions at the heavy chain CH3 interface in each half molecule to favor heterodimer formation of two antibody half molecules having distinct specificity either in vitro in cell-free environment or using co-expression. The Fab arm exchange reaction is the result of a disulfide-bond isomerization reaction and dissociation-association of CH3 domains. The heavy- chain disulfide bonds in the hinge regions of the parent mono specific antibodies are reduced. The resulting free cysteines of one of the parent monospecific antibodies form an inter heavy-chain disulfide bond with cysteine residues of a second parent monospecific antibody molecule and simultaneously CH3 domains of the parent antibodies release and reform by dissociation- association. The CH3 domains of the Fab arms can be engineered to favor heterodimerization over homodimerization. The resulting product is a bispecific antibody having two Fab arms or half molecules which each binding a distinct epitope, i.e. an epitope on LTβR and an epitope on EDB of fibronectin. “Homodimerization” as used herein refers to an interaction of two heavy chains having identical CH3 amino acid sequences. “Homodimer” as used herein refers to an antibody having two heavy chains with identical CH3 amino acid sequences. “Heterodimerization” as used herein refers to an interaction of two heavy chains having non-identical CH3 amino acid sequences. “Heterodimer” as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences. The “knob-in-hole” strategy (see, e.g., PCT Publ. No. WO2006 / 028936) can be used to generate full length bispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody specifically binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody specifically binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a “hole” with the heavy chain with a “knob.” Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain, using Kabat numbering): T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S, or T366W / T366S_L368A_Y407V. Other strategies such as promoting heavy chain heterodimerization using electrostatic interactions by substituting positively charged residues at one CH3 surface and negatively charged093699.0207 PATENT residues at a second CH3 surface can be used, as described for instance in US Pat. Publ. No. US2010 / 0015133; US Pat. Publ. No. US2009 / 0182127; US Pat. Publ. No. US2010 / 028637; or US Pat. Publ. No. US2011 / 0123532. In other strategies, heterodimerization can be promoted by the following substitutions (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): L351Y_F405A_Y407V / T394W, T366I_K392M_T394W / F405A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351Y_Y407A / T366A_K409F, L351Y_Y407A / T366V K409F Y407A / T366A_K409F, or T350V_L351Y_F405A Y407V / T350V_T366L_K392L_T394W e.g. as described in U.S. Pat. Publ. No. US2012 / 0149876 or U.S. Pat. Publ. No. US2013 / 0195849. In addition to methods described above, bispecific antibodies of the invention can be generated in vitro in a cell-free environment by introducing asymmetrical mutations in the CH3 regions of two mono specific homodimeric antibodies and forming the bispecific heterodimeric antibody from two parent monospecific homodimeric antibodies in reducing conditions to allow disulfide bond isomerization according to methods described in PCT Pat. Publ. No. WO2011 / 131746. In the methods, the first monospecific bivalent antibody and the second monospecific bivalent antibody are engineered to have certain substitutions at the CH3 domain that promotes heterodimer stability; the antibodies are incubated together under reducing conditions sufficient to allow the cysteines in the hinge region to undergo disulfide bond isomerization; thereby generating the bispecific antibody by Fab arm exchange. The incubation conditions can optionally be restored to non-reducing conditions. Exemplary reducing agents that can be used are 2-mercaptoethylamine (2-MEA), dithiothreitol (DTT), dithioerythritol (DTE), glutathione, tris (2-carboxyethyl) phosphine (TCEP), L-cysteine and beta-mercaptoethanol, preferably a reducing agent selected from the group consisting of: 2-mercaptoethylamine, dithiothreitol and tris (2-carboxyethyl) phosphine. For example, incubation for at least 90 min at a temperature of at least 20 °C in the presence of at least 25 mM 2-MEA or in the presence of at least 0.5 mM dithiothreitol at a pH from 5-8, for example at pH of 7.0 or at pH of 7.4 can be used. In some embodiments described herein, immune effector properties of the multispecific binding molecules such as bispecific antibodies of the invention can be modified, preferably silenced, e.g. through Fc modifications by techniques known to those skilled in the art. For example, Fc effector functions such as Clq binding, complement dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. can be provided and / or controlled by modifying residues in the Fc responsible for these activities,093699.0207 PATENT see, e.g., N297 mutations in Nose et al., PNAS (1983); LALA mutations in Xu et al., Cell Immunol. 200(1):16-26) (2000); and DANA mutations in Wilson et al., Cancer Cell 19(1):101-113 (2011); or e.g. mutations of aspartic acid (D) at position 265, asparagine (N) at position 297 and proline (P) at position 329, wherein numbering is indicated by the EU index as in Kabat, e.g. each to alanine (A) to get a so-called DANAPA mutant, as described in detail in WO 2019 / 068632. “Antibody-dependent cell-mediated cytotoxicity” or “ADCC” refers to a cell-mediated reaction in which non-specific cytotoxic cells that express Fc receptors (FcRs) (e.g. Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell. In certain embodiments, the multispecific binding molecule of the invention comprises a bispecific antibody that is chimeric. In certain embodiments, the multispecific binding molecule of the invention comprises a bispecific antibody that is human or humanized. In certain embodiments, the multispecific binding molecule of the invention comprises constant region mutations of K248E and T437R (RE mutations) to enhance cell surface-specific antibody clustering and LTβR agonism (Zhang, D. et al. Functional optimization of agonistic antibodies to OX40 receptor with novel Fc mutations to promote antibody multimerization. MAbs 9, 1129-1142, doi:10.1080 / 19420862.2017.1358838 (2017)). In another general aspect, the invention relates to one or more nucleic acids encoding a multispecific binding molecule, e.g. bispecific antibody or antigen-binding fragment thereof of the invention. By way of a non-limiting example, a heavy chain for a bispecific antibody can be encoded by one nucleic acid, and a light chain can be encoded by a second nucleic acid. In another example, a heavy chain and a light chain of a bispecific antibody may be encoded on a single nucleic acid molecule. It will be appreciated by those skilled in the art that the coding sequence of a protein can be changed (e.g., replaced, deleted, inserted, etc.) without changing the amino acid sequence of the protein in view of the degeneracy of the genetic code. Accordingly, it will be understood by those skilled in the art that nucleic acid sequences encoding monoclonal antibodies and / or bispecific antibodies of the invention can be altered without changing the amino acid sequences of the proteins. Additionally, the one or more nucleic acids of the invention can be isolated nucleic acids. Accordingly, the invention relates to any nucleic acid molecule or combination of nucleic acid molecules encoding a molecule of the invention. In another general aspect, the invention relates to one or more vectors comprising the one or more nucleic acids of the invention. Any vector known to those skilled in the art in view of the present disclosure can be used, such as a plasmid, a cosmid, a phage vector or a viral vector. In093699.0207 PATENT some embodiments, the vector is a recombinant expression vector such as a plasmid. The vector can include any element to establish a conventional function of an expression vector, for example, a promoter, ribosome binding element, terminator, enhancer, selection marker, and / or origin of replication. The promoter can be a constitutive, inducible or repressible promoter. A number of expression vectors capable of delivering nucleic acids to a cell are known in the art and can be used herein for production of an antibody or antigen-binding fragment thereof in the cell. Conventional cloning techniques or artificial gene synthesis can be used to generate a recombinant expression vector according to embodiments of the invention. Such techniques are well known to those skilled in the art in view of the present disclosure. In another general aspect, the invention relates to a host cell comprising the one or more vectors comprising the one or more nucleic acids encoding a multispecific binding molecule such as a bispecific antibody or an antigen-binding fragment thereof of the invention. Any host cell known to those skilled in the art in view of the present disclosure can be used for recombinant expression of multispecific binding molecules such as bispecific antibodies or antigen-binding fragments thereof of the invention. In some embodiments, the host cells are E. coli TG1 or BL21 cells (for expression of, e.g., an scFv or Fab antibody), CHO-DG44 or CHO-K1 cells or HEK293 cells (for expression of, e.g., a full-length IgG antibody). According to particular embodiments, the recombinant expression vector is transformed into host cells by conventional methods such as chemical transfection, heat shock, or electroporation, where it can be stably integrated into the host cell genome such that the recombinant nucleic acid is effectively expressed. In another general aspect, the invention relates to a method of producing a multispecific binding molecule such as a bispecific antibody or antigen-binding fragment thereof disclosed herein. The methods comprise culturing a cell comprising a nucleic acid encoding the multispecific binding molecule such as a bispecific antibody or antigen-binding fragment thereof under conditions to produce a multispecific binding molecule such as a bispecific antibody or antigen- binding fragment thereof disclosed herein and recovering the multispecific binding molecule such as a bispecific antibody or antigen-binding fragment thereof from the cell or cell culture (e.g., from the supernatant). Expressed multispecific binding molecule such as bispecific antibodies or antigen-binding fragments thereof can be harvested from the cells and purified according to conventional techniques known in the art and as described herein. Non-limiting Exemplary Antibodies In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH093699.0207 PATENT comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 251. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2197. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 474. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2198. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH093699.0207 PATENT comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 5. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 762, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 763; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 730. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 29. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 496. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2221. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 273. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2222. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy093699.0207 PATENT chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 770; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 773. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 34 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 278 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2227. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 501 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2228. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 798; and the VL comprises an LCDR1 comprising093699.0207 PATENT the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 801. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 46. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 288 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 290. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2241. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 511 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 513. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2242. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 727; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 767.093699.0207 PATENT In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 276 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2225. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising a heavy chain variable region (VH) and a light chain variable region (VL). In certain embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO: 499 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500. In certain embodiments, the present disclosure provides an antibody or an antigen binding fragment thereof comprising a binding domain that specifically binds to LTβR comprising the amino acid sequence set forth in SEQ ID NO: 2226. In certain embodiments, the present disclosure provides a multispecific binding molecule comprising a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof. In certain embodiments, the binding domain that specifically binds to LTβR comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (a) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701; (b) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 762, and an093699.0207 PATENT HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 763; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 770; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 773; (d) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 798; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 801; or (e) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 727; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 767. In certain embodiments, the binding domain that specifically binds to LTβR comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (a) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 251; (b) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 474; (c) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 5; (d) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 29; (e) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 496;093699.0207 PATENT (f) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 273; (g) the VH comprises the amino acid sequence set forth in SEQ ID NO: 34 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (h) the VH comprises the amino acid sequence set forth in SEQ ID NO: 278 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; (i) the VH comprises the amino acid sequence set forth in SEQ ID NO: 501 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500; (j) the VH comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 46; (k) the VH comprises the amino acid sequence set forth in SEQ ID NO: 288 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 290; (l) the VH comprises the amino acid sequence set forth in SEQ ID NO: 511 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 513; (m) the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (n) the VH comprises the amino acid sequence set forth in SEQ ID NO: 276 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; or (o) the VH comprises the amino acid sequence set forth in SEQ ID NO: 499 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500. In certain embodiments, the binding domain that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226. In certain embodiments, the binding domain that specifically binds to EDB comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 704; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 707.093699.0207 PATENT In certain embodiments, the binding domain that specifically binds to EDB comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 6 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 7. LTBR509 / AGB201 In certain embodiments, the presently disclosed multispecific binding molecule comprising a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof is designated as “AGB201” or “LTBR509.” Additionally or alternatively, the AGB201 can also be designated as “COVA1417,” “40763p1.E9,” “40763 E9,” “E9,” or “LTBR-E9.” In certain embodiments, the AGB201 comprises a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof, wherein: (a) the binding domain that specifically binds to LTβR comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701; and (b) the binding domain that specifically binds to EDB comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 704; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 707. In certain embodiments, the AGB201 comprises a multispecific binding molecule comprising a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof, wherein: (a) the binding domain that specifically binds to LTβR comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 250 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 251; and093699.0207 PATENT (b) the binding domain that specifically binds to EDB comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 6 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the AGB201 comprises (a) the binding domain that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2197; and the binding domain that specifically binds to EDB comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 6 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 7. In certain embodiments, the AGB201 comprises a heavy chain (HC) and a light chain (LC). In certain embodiments, the HC comprises the amino acid sequence set forth in SEQ ID NO: 2174 and the LC comprises the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, the AGB201 comprises a first heavy chain (HC1), a second heavy chain (HC2), a first light chain (LC1), and a second light chain (LC2). In certain embodiments, each of HC1 and HC2 comprises the amino acid sequence set forth in SEQ ID NO: 2174 and each of LC1 and LC2 comprises the amino acid sequence set forth in SEQ ID NO: 2087. LTBR146 In certain embodiments, the present disclosure provides a multispecific binding molecule that specifically binds to LTβR and EDB comprising a heavy chain (HC) and a light chain (LC). In certain embodiments, the HC comprises the amino acid sequence set forth in SEQ ID NO: 2105 or 2486 and the LC comprises the amino acid sequence set forth in SEQ ID NO: 2087. In certain embodiments, the present disclosure provides a multispecific binding molecule that specifically binds to LTβR and EDB comprising a first heavy chain (HC1), a second heavy chain (HC2), a first light chain (LC1), and a second light chain (LC2). In certain embodiments, each of HC1 and HC2 comprises the amino acid sequence set forth in SEQ ID NO: 2105 or 2486 and each of LC1 and LC2 comprises the amino acid sequence set forth in SEQ ID NO: 2087. Exemplary Amino Acid Sequences

[0001] SEQ ID Nos: 6, 7, 250, 251,2087, 2105, 2174, and 2486 are provided below:EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSISGSSGTTYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSS [SEQ ID NO: 6] EIVLTQSPGTLSLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIYYASSRATGIPDRFSG SGSGTDFTLTISRLEPEDFAVYYCQQTGRIPPTFGQGTKVEIK [SEQ ID NO: 7]093699.0207 PATENT EVQLLESGGGLVQPGGSLRLSCVASRFTFSNYIMTWVRQAPGKGLDWVSTISGSGDATYYADSVK GRFTISRDNSKNMLYLQMNSLRAEDTALYYCAKHITGPTYDYYGMDVWGCGTTVTVSS [SEQ ID NO: 250] QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGCAPKLLIYLNSQRPSGVPDRFSG SKSGTSASLAISGLQSEDEADYYCATWEGGLNVWVFGGGTKLTVL [SEQ ID NO: 251] EIVLTQSPGTLSLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIYYASSRATGIPDRFSG SGSGTDFTLTISRLEPEDFAVYYCQQTGRIPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC EVTHQGLSSPVTKSFNRGEC [SEQ ID NO: 2087] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSISGSSGTTYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGS GGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGCAPKLLIYLNSQR PSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCATWEGGLNVWVFGGGTKLTVLGGGSGGSGGC PPCGGSGGEVQLLESGGGLVQPGGSLRLSCVASRFTFSNYIMTWVRQAPGKGLDWVSTISGSGDA TYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTALYYCAKHITGPTYDYYGMDVWGCGTTVTVS S [SEQ ID NO: 2105] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSISGSSGTTYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG SGGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGCAPKLLIYLNSQ RPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCATWEGGLNVWVFGGGTKLTVLGGGSGGSGG CPPCGGSGGEVQLLESGGGLVQPGGSLRLSCVASRFTFSNYIMTWVRQAPGKGLDWVSTISGSGD093699.0207 PATENT ATYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTALYYCAKHITGPTYDYYGMDVWGCGTTVTV SSH [SEQ ID NO: 2174] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSFSMSWVRQAPGKGLEWVSSISGSSGTTYYADSVK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKPFPYFDYWGQGTLVTVSSASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVSVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG SGGGGSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVSWYQQLPGCAPKLLIYLNSQ RPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCATWEGGLNVWVFGGGTKLTVLGGGSGGSGG CPPCGGSGGEVQLLESGGGLVQPGGSLRLSCVASRFTFSNYIMTWVRQAPGKGLDWVSTISGSGD ATYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTALYYCAKHITGPTYDYYGMDVWGCGTTVTV SS [SEQ ID NO: 2486] Pharmaceutical Compositions In another general aspect, the invention relates to a pharmaceutical composition comprising a multispecific binding molecule (e.g., a bispecific antibody or antigen-binding fragment thereof) of the invention and a pharmaceutically acceptable carrier. The term “pharmaceutical composition” as used herein means a product comprising a multispecific binding molecule of the invention together with a pharmaceutically acceptable carrier. Multispecific binding molecules (e.g., bispecific antibodies) of the invention and compositions comprising them are also useful in the manufacture of a medicament for therapeutic applications mentioned herein. As used herein, the term “carrier” refers to any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, oil, lipid, lipid containing vesicle, microsphere, liposomal encapsulation, or other material well known in the art for use in pharmaceutical formulations. It will be understood that the characteristics of the carrier, excipient, or diluent will depend on the route of administration for a particular application. As used herein, the term “pharmaceutically acceptable carrier” refers to a non-toxic material that does not interfere with the effectiveness of a composition according to the invention or the biological activity of a composition according to the invention. According to particular embodiments, in view of the present disclosure, any pharmaceutically acceptable carrier suitable for use in an antibody pharmaceutical composition can be used herein.093699.0207 PATENT The formulation of pharmaceutically active ingredients with pharmaceutically acceptable carriers is known in the art, e.g., Remington: The Science and Practice of Pharmacy (e.g. 21stedition (2005), and any later editions). Non-limiting examples of additional ingredients include: buffers, diluents, solvents, tonicity regulating agents, preservatives, stabilizers, and chelating agents. One or more pharmaceutically acceptable carriers can be used in formulating the pharmaceutical compositions of the invention. In one embodiment of the invention, the pharmaceutical composition is a liquid formulation. A preferred example of a liquid formulation is an aqueous formulation, i.e., a formulation comprising water. The liquid formulation can comprise a solution, a suspension, an emulsion, a microemulsion, a gel, and the like. An aqueous formulation typically comprises at least 50% w / w water, or at least 60%, 70%, 75%, 80%, 85%, 90%, or at least 95% w / w of water. In one embodiment, the pharmaceutical composition can be formulated as an injectable which can be injected, for example, via an injection device (e.g., a syringe or an infusion pump). The injection can be delivered subcutaneously, intramuscularly, intraperitoneally, intravitreally, or intravenously, for example. In another embodiment, the pharmaceutical composition is a solid formulation, e.g., a freeze-dried or spray-dried composition, which can be used as is, or whereto the physician or the patient adds solvents, and / or diluents prior to use. Solid dosage forms can include tablets, such as compressed tablets, and / or coated tablets, and capsules (e.g., hard or soft gelatin capsules). The pharmaceutical composition can also be in the form of sachets, dragees, powders, granules, lozenges, or powders for reconstitution, for example. The dosage forms can be immediate release, in which case they can comprise a water- soluble or dispersible carrier, or they can be delayed release, sustained release, or modified release, in which case they can comprise water-insoluble polymers that regulate the rate of dissolution of the dosage form in the gastrointestinal tract or under the skin. In other embodiments, the pharmaceutical composition can be delivered intranasally, intrabuccally, or sublingually. The pH in an aqueous formulation can be between pH 3 and pH 10. In one embodiment of the invention, the pH of the formulation is from about 7.0 to about 9.5. In another embodiment of the invention, the pH of the formulation is from about 3.0 to about 7.0. In certain embodiments, the pharmaceutical composition comprises a buffer. Non-limiting examples of buffers include: arginine, aspartic acid, bicine, citrate, disodium hydrogen phosphate, fumaric acid, glycine, glycylglycine, histidine, lysine, maleic acid, malic acid, sodium acetate, sodium carbonate, sodium dihydrogen phosphate, sodium phosphate, succinate, tartaric acid,093699.0207 PATENT tricine, or tris(hydroxymethyl)-aminomethane, and mixtures thereof. The buffer can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific buffers constitute alternative embodiments of the invention. In certain embodiments, the pharmaceutical composition comprises a preservative. Non- limiting examples of preservatives include: benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butyl 4-hydroxybenzoate, chlorobutanol, chlorocresol, chlorohexidine, chlorphenesin, o-cresol, m-cresol, p-cresol, ethyl 4-hydroxybenzoate, imidurea, methyl 4-hydroxybenzoate, phenol, 2-phenoxyethanol, 2-phenylethanol, propyl 4-hydroxybenzoate, sodium dehydroacetate, thiomerosal, and mixtures thereof. The preservative can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific preservatives constitute alternative embodiments of the invention. In certain embodiments, the pharmaceutical composition comprises an isotonic agent. Non- limiting examples of isotonic agents include a salt (such as sodium chloride), an amino acid (such as glycine, histidine, arginine, lysine, isoleucine, aspartic acid, tryptophan, or threonine), an alditol (such as glycerol, 1,2-propanediol propyleneglycol), 1,3-propanediol, or 1,3-butanediol), polyethyleneglycol (e.g. PEG400), and mixtures thereof. Another example of an isotonic agent includes a sugar. Non-limiting examples of sugars can include mono-, di-, or polysaccharides, or water-soluble glucans, including for example fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, pullulan, dextrin, cyclodextrin, alpha and beta- HPCD, soluble starch, hydroxyethyl starch, or sodium carboxymethyl-cellulose. Another example of an isotonic agent is a sugar alcohol, wherein the term “sugar alcohol” is defined as a C(4-8) hydrocarbon having at least one -OH group. Non-limiting examples of sugar alcohols include mannitol, sorbitol, inositol, galactitol, dulcitol, xylitol, or arabitol. The isotonic agent can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific isotonic agents constitute alternative embodiments of the invention. In certain embodiments, the pharmaceutical composition comprises a chelating agent. Non- limiting examples of chelating agents include citric acid, aspartic acid, salts of ethylenediaminetetraacetic acid (EDTA), and mixtures thereof. The chelating agent can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific chelating agents constitute alternative embodiments of the invention.093699.0207 PATENT In certain embodiments, the pharmaceutical composition comprises a stabilizer. Non- limiting examples of stabilizers include one or more aggregation inhibitors, one or more oxidation inhibitors, one or more surfactants, and / or one or more protease inhibitors. In certain embodiments, the pharmaceutical composition comprises a stabilizer, wherein said stabilizer is carboxy- / hydroxycellulose and derivates thereof (such as HPC, HPC-SL, HPC-L and HPMC), cyclodextrins, 2-methylthioethanol, polyethylene glycol (such as PEG 3350), polyvinyl alcohol (PVA), polyvinyl pyrrolidone, salts (such as sodium chloride), sulfur-containing substances such as monothioglycerol), or thioglycolic acid. The stabilizer can be present individually or in the aggregate, in a concentration from about 0.01 mg / ml to about 50 mg / ml, for example from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific stabilizers constitute alternative embodiments of the invention. In certain embodiments, the pharmaceutical composition comprises one or more surfactants. The term “surfactant” refers to any molecules or ions that are comprised of a water- soluble (hydrophilic) part, and a fat-soluble (lipophilic) part. The surfactant can, for example, be selected from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants, and / or zwitterionic surfactants. The surfactant can be present individually or in aggregate, in a concentration from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific surfactants constitute alternative embodiments of the invention. In certain embodiments, the pharmaceutical composition comprises one or more protease inhibitors, such as, e.g., EDTA, and / or benzamidine hydrochloric acid (HCl). The protease inhibitor can be present individually or in the aggregate, in a concentration from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific protease inhibitors constitute alternative embodiments of the invention. In another general aspect, the invention relates to a method of producing a pharmaceutical composition comprising a multispecific binding molecule such as a bispecific antibody or antigen- binding fragment thereof of the invention, comprising combining a multispecific binding molecule such as a bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. Methods of use In another general aspect, the invention relates to a method of targeting LTβR on cells present in tumors (e.g., tumor cells, fibroblasts, monocytes, etc.), the method comprising exposing the cells present in tumors to a multispecific binding molecule or a pharmaceutical composition of the invention.093699.0207 PATENT The functional activity of multispecific binding molecules (e.g., bispecific antibodies and antigen-binding fragments thereof) that bind LTβR and / or EDB, MSLN, PSMA, or EGFR can be characterized by methods known in the art and as described herein. Methods for characterizing the multispecific binding molecules that bind LTβR and / or EDB include, but are not limited to, affinity and specificity assays including Biacore, ELISA, and / or OctetRed analysis; binding assays to detect the binding of the multispecific binding molecules to LTβR on cancer cells and other cell types by FACS. According to particular embodiments, the methods for characterizing multispecific binding molecules that bind LTβR and / or EDB include those described below. In another general aspect, the invention relates to a method to establish a pro-inflammatory tumor microenvironment. The methods comprise contacting the LTβR-expressing cells in the tumor microenvironment with a multispecific binding molecule of the invention, wherein contacting the LTβR-expressing cells with the multispecific binding molecule leads to the secretion of pro-inflammatory chemokines and cytokines and expression of adhesion molecules on the cell surface. In another general aspect, the invention relates to a method of treating a cancer in a subject in need thereof, comprising administering to the subject a multispecific binding molecule of the invention (e.g., a bispecific antibody or antigen binding fragment thereof) that specifically binds LTβR and EDB of fibronectin, or a pharmaceutical composition disclosed herein. The cancer preferably is an EDB-expressing cancer. The cancer can, for example, be an LTβR-expressing cancer. The cancer can, for example, be selected from the group consisting of a prostate cancer, a lung cancer, a gastric cancer, an esophageal cancer, a bile duct cancer, a cholangiocarcinoma, a colon cancer, a hepatocellular carcinoma, a renal cell carcinoma, a bladder urothelial carcinoma, a metastatic melanoma, a breast cancer, an ovarian cancer, a cervical cancer, a head and neck cancer, a pancreatic cancer, a glioma, a glioblastoma, and other solid tumors, and a non-Hodgkin’s lymphoma (NHL), an acute lymphocytic leukemia (ALL), a chronic lymphocytic leukemia (CLL), a chronic myelogenous leukemia (CML), a multiple myeloma (MM), an acute myeloid leukemia (AML), and other liquid tumors. In certain embodiments, the cancer is a lung cancer. Non-limiting examples of lung cancer include small cell lung cancer, non small cell lung cancer (NSCLC), adenocarcinoma, squamous lung cancer and / or carcinoma, and large cell carcinoma. In certain embodiments, the lung cancer is a small cell lung cancer. In certain embodiments, the lung cancer is an adenocarcinoma. In certain embodiments, the lung cancer is a squamous lung cancer. In certain embodiments, the cancer is a bladder cancer. Non-limiting examples of bladder cancer include urinary bladder cancer, metastatic bladder cancer, muscle invasive bladder cancer,093699.0207 PATENT and non-invasive bladder cancer. In certain embodiments, the bladder cancer is a urinary bladder cancer. In certain embodiments, the bladder cancer is a metastatic bladder cancer. In certain embodiments, the bladder cancer is a muscle invasive bladder cancer. In certain embodiments, the bladder cancer is a non-invasive bladder cancer. In certain embodiments, the cancer is a head and neck cancer. Non-limiting examples of head and neck cancer include oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, laryngeal cancer, hypopharyngeal cancer, salivary gland cancer, nasal cavity, or paranasal sinus cancer. In certain embodiments, the head and neck cancer is a pharynx cancer. In certain embodiments, the head and neck cancer is a larynx cancer. In certain embodiments, the head and neck cancer is an oral cavity cancer. In certain embodiments, the cancer is an esophageal cancer. In certain embodiments, the cancer is a vaginal cancer. In certain embodiments, the vaginal cancer is a cancer of the vulva. In certain embodiments, the vaginal cancer is a cancer of the vagina. In certain embodiments, the vaginal cancer is a cancer of the cervix. In certain embodiments, the cancer is a pancreatic cancer. In certain embodiments, the cancer is a colon cancer. In certain embodiments, the cancer is a colorectal cancer, a cancer of the small intestines, a gastrointestinal cancer, or a rectal cancer. In certain embodiments, the cancer is a liver cancer. In certain embodiments, the cancer is a uterine cancer. In certain embodiments, the cancer is an ovarian cancer. In certain embodiments, the cancer is a breast cancer. In certain embodiments, the cancer is a prostate cancer. In certain embodiments, the cancer is a stomach cancer. In certain embodiments, the cancer is melanoma. In certain embodiments, the cancer is glioblastoma (GBM). In certain embodiments, the cancer is an endometrial cancer. In certain embodiments, the cancer is a soft tissue carcinoma. In certain embodiments, the cancer is a mesothelioma. In certain embodiments, the cancer has a high prevalence of EDB expression. According to embodiments of the invention, the pharmaceutical composition comprises an effective amount of an anti-LTΒR multispecific binding molecule (e.g., an anti-LTΒR × anti-EDB bispecific antibody or antigen-binding fragment thereof). As used herein, the term “effective amount” refers to an amount of an active ingredient or component that elicits the desired biological or medicinal response in a subject. According to particular embodiments, an effective amount refers to the amount of therapy which is sufficient to achieve one, two, three, four, or more of the following effects: (i) reduce or ameliorate the severity of the disease, disorder or condition to be treated or a symptom associated therewith; (ii) reduce the duration of the disease, disorder or condition to be treated, or a symptom093699.0207 PATENT associated therewith; (iii) prevent the progression of the disease, disorder or condition to be treated, or a symptom associated therewith; (iv) cause regression of the disease, disorder or condition to be treated, or a symptom associated therewith; (v) prevent the development or onset of the disease, disorder or condition to be treated, or a symptom associated therewith; (vi) prevent the recurrence of the disease, disorder or condition to be treated, or a symptom associated therewith; (vii) reduce hospitalization of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (viii) reduce hospitalization length of a subject having the disease, disorder or condition to be treated, or a symptom associated therewith; (ix) increase the survival of a subject with the disease, disorder or condition to be treated, or a symptom associated therewith; (xi) inhibit or reduce the disease, disorder or condition to be treated, or a symptom associated therewith in a subject; and / or (xii) enhance or improve the prophylactic or therapeutic effect(s) of another therapy. In certain embodiments, the multispecific binding molecule of the disclosure comprises mutations at the lysine at position 248 (K248, EU numbering) and the threonine at position 437 (T437, EU numbering) in the Fc region. Lysine at position 248 (K248, EU numbering) and threonine at position 437 (T437, EU numbering) are both conserved residues in the Fc regions among different IgG subtypes (Zhang, D., et al., supra). Fc mutations, T437R and K248E (EU numbering), were shown to facilitate oligomerization of antibodies upon binding antigens at the cell surface (Zhang, D., et al., supra). In some embodiments, multispecific binding molecules comprising K248E and T437R (RE mutations) have enhanced cell surface-specific antibody clustering and LTβR agonism. In some embodiments, clustering of antibodies enhances signaling and / or drives signaling towards non-canonical NF-κB signaling. In some embodiments, clustering of antibodies drives pro-tertiary lymphoid structure (TLS) pathways and / or encourages TLS neogenesis. In some embodiments, the multispecific binding molecule is divalent for LTβR (i.e., has two LTβR-binding domains), which further drives pro-TLS pathways and / or encourages TLS neogenesis. The presence of tumor-associated TLS is associated with more favorable prognosis in cancer patients and response to immune checkpoint therapies, providing advantages over specific immune cell subset immunotherapies (e.g. T cell redirection), since it leads to infiltration of a diverse immune repertoire, including both innate and adaptive immune cells, that is more likely to overcome immune resistance. In some embodiments, the effective amount of multispecific binding molecule of the invention may be administered at a dose in the range from about 0.1 mg / kg to about 25 mg / kg, about 0.1 mg / kg to about 20 mg / kg, about 0.1 mg / kg to about 15 mg / kg, about 0.1 mg / kg to about 10 mg / kg, or about 0.1 mg / kg to about 5 mg / kg.093699.0207 PATENT The effective amount or dosage can vary according to various factors, such as the disease, disorder or condition to be treated, the means of administration, the target site, the physiological state of the subject (including, e.g., age, body weight, health), whether the subject is a human or an animal, other medications administered, and whether the treatment is prophylactic or therapeutic. Treatment dosages are optionally titrated to optimize safety and efficacy. According to particular embodiments, the compositions described herein are formulated to be suitable for the intended route of administration to a subject. For example, the compositions described herein can be formulated to be suitable for intravenous, subcutaneous, or intramuscular administration. In some embodiments, the compositions disclosed herein may be administered to a subject by a variety of routes such as topical, oral or parenterally. Methods of parenteral delivery include intra-arterial (directly to the tissue), intramedullary, intrathecal, intraventricular, intraperitoneal, or intranasal administration. As used herein, the terms “treat,” “treating,” and “treatment” are all intended to refer to an amelioration or reversal of at least one measurable physical parameter related to a cancer, which is not necessarily discernible in the subject, but can be discernible in the subject. The terms “treat,” “treating,” and “treatment,” can also refer to causing regression, preventing the progression, or at least slowing down the progression of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an alleviation, prevention of the development or onset, or reduction in the duration of one or more symptoms associated with the disease, disorder, or condition, such as a tumor or more preferably a cancer. In a particular embodiment, “treat,” “treating,” and “treatment” refer to prevention of the recurrence of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an increase in the survival of a subject having the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to elimination of the disease, disorder, or condition in the subject. According to particular embodiments, provided are compositions used in the treatment of a cancer. For cancer therapy, the compositions can be used in combination with another treatment including, but not limited to, a chemotherapy, an anti-CD20 mAb, an anti-TIM-3 mAb, an anti- CTLA-4 antibody, an anti-PD-L1 antibody, an anti-PD-1 antibody, a PD-1 / PD-L1 therapy, Indoleamine-pyrrole 2,3-dioxygenase (IDO), an anti-OX40 antibody, an anti-GITR antibody, an anti-CD40 antibody, an anti-CD38 antibody, cytokines, oncolytic viruses, TLR agonists, STING agonist, other immuno-oncology drugs, an antiangiogenic agent, a radiation therapy, an antibody- drug conjugate (ADC), a targeted therapy, or other anticancer drugs.093699.0207 PATENT As used herein, the term “in combination,” in the context of the administration of two or more therapies to a subject, refers to the use of more than one therapy. The use of the term “in combination” does not restrict the order in which therapies are administered to a subject. For example, a first therapy (e.g., a composition described herein) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of a second therapy to a subject. In certain embodiments, the disclosure provides methods of driving signaling towards non- canonical NF-κB signaling, promoting pro-TLS pathways, and / or encouraging TLS neogenesis in a subject. In some embodiments, the method comprises administering to the subject a binding molecule that is at least divalent for LTβR (i.e., has at least two binding domains that specifically bind to LTβR). In some embodiments, the binding molecule further comprises mutations at the lysine at position 248 (K248, EU numbering) and the threonine at position 437 (T437, EU numbering) in the Fc region. In some embodiments, binding molecules comprising K248E and T437R (RE mutations) have further enhanced cell surface-specific antibody clustering and LTβR agonism. The presence of tumor-associated TLS is associated with more favorable prognosis in cancer patients and response to immune checkpoint therapies, providing advantages over specific immune cell subset immunotherapies (e.g. T cell redirection), since it leads to infiltration of a diverse immune repertoire, including both innate and adaptive immune cells, that is more likely to overcome immune resistance. EXAMPLES The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the invention, and not by way of limitation. Example 1. Antibody Generation and Protein Design Generation and characterization of anti-LTΒR antibodies from primary chicken B cells Anti-LTΒR human monoclonal antibodies were generated using transgenic chickens (OmniChicken™) that express human antibody genes: human light chain (VLCL or VKCK) and human VH while expressing the chicken constant regions of the heavy chain (Ching, KH et. Al (2018). Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets, mAbs, 10:1, 71-80).093699.0207 PATENT Ten transgenic chickens (OmniChicken™) were immunized with 100 µg of Fc-tagged human LTβR-iso 1 (SEQ ID NO: 1) every 14 days for up to 10 weeks. The serum immune response was monitored by ELISA. Splenocytes were isolated and tested using the GEM assay (as described in Mettler Izquierdo et al 2016). Briefly, large beads (Life Technologies # A37306) were coated with Fc- tagged cynomolgus LTβR X2 (SEQ ID NO: 2), smaller beads (Life Technologies # A37296) were coated with Fc-tagged mouse LTβR-iso 1 (SEQ ID NO:3), and blue beads were coated with Fc- tagged DcR3 (R&D Systems cat# 142-DC-100), Fc-tagged CD40 (Novoprotein cat# CD12), and Fc-tagged HVEM (Biolegend cat# 596506) overnight. Beads were blocked in 3% milk in DPBS for 1 h at room temperature then washed three times in DPBS. Beads were mixed in the ratio 5:1 (small over large beads) with 1 × 107primary splenocytes and an Alexa FluorTM594-conjugated goat anti-chicken IgY (Thermo Fisher Scientific cat# A-11042) for the detection. The mixture was plated, and positive clones were detected under microscope using a triple filter (blue, green, red). Cells secreting IgY that bound to the cynomolgus LTβR X2 and mouse LTβR-iso 1 beads were selected. Positive clones were transferred into a 96-well plate containing a PCR mixture consisting of dNTP, primers, and enzyme mix. The variable regions of heavy and light chains were cloned and assembled into a single chain Fv-Fc (ScFv-Fc) mammalian expression vector. Sanger sequencing was performed by GeneWiz and sequences were evaluated using DNASTAR Lasergene 15. Unique scFv-Fcs were transiently expressed in Expi293 cells (Life Technologies, #A14527) grown in Expi293 Expression Medium (Life Technologies, #A1435101) after transfection using the ExpiFectamineTMtransfection reagent and supplements (Life Technologies, #A14524). Cells were incubated for 3-5 days with shaking at 37 °C in a 5% CO2 humidified incubator. Supernatants were harvested, quantitated using a Blitz Instrument (Pall ForteBio), and tested for binding activity by ELISA on plates coated with His-tagged human LTΒR-iso 1 (Covagen), His-tagged human LTΒR-iso 2 (Covagen), His-tagged cynomolgus LTΒR-X2 (Covagen) , His-tagged mouse LTΒR-iso 1 (Covagen), His-tagged human DcR3 (Creative BioMart, cat# TNSFF6B-552H), His-tagged human CD40 (Acro Biosystems, cat# CD0-H5228), and His-tagged human HVEM (Acro Biosystems, cat# HVM-H52E9). A total of 35 antibodies showed cross reactivity to the three species and 90 antibodies bound to human and cynomolgus LTΒR. Binding of anti-LTΒR antibodies to cell lines was assessed by FACS. Briefly, approximately 1.5 × 105HT29 or NCI-H1299 cells were resuspended in FACS buffer (PBS, 1% BSA, 0.1% sodium azide) containing 10 µg / ml of anti-LTΒR antibodies and incubated for 60 min093699.0207 PATENT at 4 °C. Cells were washed and resuspended in FACS buffer containing Alexa Fluor 647 AffiniPure Donkey anti-human Fc (Jackson ImmunoResearch Laboratories, cat# 709-605-098) for 60 min at 4 °C. Cells were then centrifuged and resuspended in FACS buffer. Analysis was done on an Attune Flow Cytometer from Invitrogen. Histograms (fluorescence vs count) were plotted. Binding affinities and epitope bins of anti-LTΒR antibodies to LTβR were determined by Surface Plasmon Resonance (SPR) using an LSA instrument (Carterra, Inc.). For binding affinities, goat anti-human Fc antibody was amine coupled to an HC30M chip. Anti-LTΒR supernatants were diluted 30-fold with HBSTE and were captured by the anti-human Fc coupled HC30M chip. Dilution series, starting at 400 nM His-tagged LTβR followed by 1:2 dilution for a total of 8 concentrations, were injected to the chip for binding. Binding affinities were determined for human, mouse, and cynomolgus monkey. For epitope binning, supernatants containing anti-LTΒR antibodies (ligand) were diluted 50-fold and coupled to an HC2000M chip via sulfo-NHS / EDC coupling and blocked with ethanolamine. In each cycle of the binning experiment, 100 nM His- tagged human LTβR-iso 1 was injected to the whole array and then an individual supernatant anti- LTΒR (analyte), diluted 40-fold in HBSTE+BSA, was injected to the whole array to sandwich the antigen bound to the ligand scFv-Fc. LIGHT or LTα1b2 was also injected as an analyte to determine the anti-LTΒR antibodies ability to block ligand binding to the receptor. At the end of each cycle the chip was regenerated with 10 mM Glycine at pH 2. Activity of the of anti-LTΒR antibodies was determine using the NF-κB Reporter – A549 Recombinant Stable Cell Line (BPS Bioscience cat# 60625). Briefly, Greiner high-binding plates (VWR cat# 82050-720) were coated with anti-human Fc (VWR cat# RL609-4103) at 40 nM overnight at 4 °C. The plates were washed three times and blocked with complete media (DMEM medium, 10% FBS, 1% Penicillin / Streptomycin, 1 mg / ml G418 Sulfate) for 1 hour at room temperature. Block was removed and 50 µl of anti-LTΒR antibodies or LIGHT (R&D Systems, RDSY664-LI-025 / CF; fivefold dilutions over eight wells, stating at 40 nM) was added to the plates for 1 hour at room temperature. Two hundred thousand A549 recombinant stable cells in 50 µl were added were added to each well. Plates were incubated overnight at 37 °C, in 5% CO2 humidified incubator for 18-20 hours. For development, an equal volume (100 µl) of Promega’s Bio-Glo Luciferase Assay System (VWR cat# PAG7940) was added to each well with robust pipetting. Plates were vigorously shaken for 10 min followed by a second round of robust pipetting. Lysate was transferred to a solid white plate (VWR cat# 89091-016) and luminescence was read on a Biotek Synergy H1. Data analysis was performed using Prism 8 GraphPad. Generation and characterization of anti-LTΒR antibodies by llama immunization and panning of VHH immune phage display libraries093699.0207 PATENT Antibodies were generated by either panning against a naïve phage displayed library or by immunizing llamas with recombinant human LTβR-Fc followed by panning on recombinant human and cyno LTβR-Fc. Binding to recombinant LTβR was assessed by ELISA and binding to cells expressing LTβR was assessed by flow cytometry. Agonism of LTβR signaling was then assessed using an A549 reporter assay using VHH domains that displayed binding in the ELISA and flow cytometric analysis. For the identification of llama VHH antibodies specific to human ( LTβR that are cross- reactive with Cynomolgus monkey, “cyno”) LTβR, two llamas were immunized with six consecutive injections of huLTbR isoform 1 Fc recombinant protein. The llama´s immune response was evaluated via binding ELISA by titrating pre- and post-immune serum samples on coated huLTbR and cynoLTbR Fc proteins and also on HVEM-Fc protein. Overall, higher immune responses were observed for llama SPTL13 compared to llama SPTL12 and an immune response was observed to the huHVEM-Fc protein with the pre-immune serum sample. The llama immune response was also evaluated on the human isoform 1 cynomolgus monkey LTβR and HVEM His proteins and a positive immune response was also obtained for the LTβR His tag proteins, indicating a specific immune response to LTβR and not only to the Fc tag present in the immunogen. Two llama VHH immune phage display libraries were generated from each llama with a size around 108transformants and VHH insert percentage above 97.5%, namely FL1257 SD116 (llama SPTL12) and FL1258 SD117 (llama SPTL13). For llama VHH phage display library generation, total RNA was purified from collected llama PBLs and used for cDNA synthesis using random primers. cDNA was used in a primary PCR amplification using non-tagged primers annealing at the VH leader and CH2 regions, followed by a secondary PCR amplification with primers annealing at the VHH FR1 region and the hinge region and introducing restriction endonucleases sites for cloning of VHH genes in pDCL1 phagemid. The libraries were electroporated into TG1 E. coli cells and bacterial glycerol stocks of the two llama VHH phage display libraries were stored at 80 °C. Phage produced from each of the llama VHH immune phage display libraries were used in two rounds of panning phage display selections on human LTβR isoform 1 Fc and His proteins and cyno LTβR in parallel, using huHVEM-Fc protein as counter selection, followed by a final round on HT29 cell line (endogenous expression of human LTβR). In the consecutive rounds of phage display panning selections, phage VHH were incubated with coated human or cynomolgus monkey LTβR Fc or His tagged proteins in the presence of huHVEM-Fc, and after washing of non-specific phage, specific phage were eluted with trypsin (total elution). Overall higher output093699.0207 PATENT sizes were observed for SD117 llama VHH immune library compared to SD116. Higher outputs were observed on Fc protein in comparison with His tag protein for both llama VHH immune libraries. After two rounds of phage display panning selections, enrichment values over background (1 × PBS) above 3909-fold on human and cynomolgus monkey LTβR Fc proteins and above 91-fold on human and cynomolgus monkey LTβR His protein were observed for SD116 and SD117 libraries. A third round on HT29 cell line was performed to present the antigen in the native conformation. Similar outputs were observed for llama VHH libraries SD116 and SD117 after two consecutive rounds on human or cyno LTβR Fc protein. However, after two rounds of selections on His proteins, higher output sizes were observed for outputs derived from two consecutive rounds on human LTβR protein compared to the cyno LTβR protein. Individual llama VHH clones from round two panning selection or round three cell selection condition outputs were picked into eight 96 well Master Plates (FJ1828MP07-14) and tested as monoclonal VHH periplasmic extracts (P.E.) for binding to human isoform 1 and isoform 2, cyno, and mouse LTβR proteins, HVEM, CD20, and DcR3. Proteins were detected with an anti- c-myc antibody specific to the c-myc tag present in the soluble VHHs. Overall, a higher hit rate was observed from master plates generated from SD 117 library (64 – 93%) compared to master plates generated from SD116 library (34 – 55%). One binder was identified against mouse LTβR protein from SD117 library. Both libraries showed higher hit rates for master plates generated from selections outputs derived from two consecutive rounds on His proteins (20 – 86%) compared to the selections outputs derived from two consecutive rounds on Fc proteins (12 – 60%). A low number of clones showed binding to the DcR3, CD40, and huHVEM-Fc protein. All positive VHH hits were selected for sequencing to determine the sequence diversity. A total of 565 llama VHHs clones were identified as positive binders to huLTΒR1, huLTΒR2, and / or cyno LTβR-Fc proteins, with 360 VHHs clones identified as specific clones with binding to huLTbR1, huLTbR2, and cyno LTβR-Fc proteins and no binding to the other TNFRSF proteins (CD20 and DcR3). The sequences of the 565 huLTbR1, huLTbR2, and / or cynoLTbR-Fc specific VHHs were determined by sequencing. Sequences were analyzed and extracted using CLC Main Workbench software and VHH valid sequences were classified based on identity. Furthermore, the sequences of CDR1, CDR2, and CDR3 regions from VHH sequences were extracted according to Kabat numbering and numbered based on identity. Overall, high diversity was identified from the 528 VHH valid sequences, with a total of 135 unique sequences, 59 unique sequences identified from FL1257 (SD116 library), and 76 unique sequences identified from FL1258 (SD117 library). The 135 different VHH sequences were further classified into 31 different CDR3 sequences: 19 CDR3 sequences identified from FL1257 (SD116 library) and 12093699.0207 PATENT CDR3 sequences identified from FL1258 (SD117). A total of 135 unique VHH sequence representative clones were re-arrayed into two 96-well FJ1828MP15-16 master plates for secondary screening. From the FJ1828MP15-16 master plates, P.E.s were produced and tested in different screening assays binding FACS on expressing and non-expressing cells, A549 reporter assay, LIGHT: LTβR competition ELISA, and off-rate determination by Biacore. To assess the P.E. binding to expressing and non-expressing LTΒR cell lines, P.E. binding FACS was performed on HT29 ( LTβR positive) and NCIH1299 ( LTβR negative) cell lines. Overall, higher hit rates were observed for master plates generated after a third round on HT29 cells. A total of 61 VHH clones were identified as positive binders, 25 binders (from a total of 59 clones) from SD116 library and 36 binders (from a total of 76 clones) from SD117. The clones that showed an MFI above 200 on HT29 cells were selected to proceed in the further screening assays, in a total of 91 clones. Different reporter assay set-ups for immobilized and soluble approaches were tested to establish the optimal conditions to determine the agonistic activity. Of the 91 clones tested in the immobilized set-up, 62 showed induction of LTβR signaling with ligand-like activity showing a fold induction > 2.0 compared to the unstimulated cells. To further screen the isolated VHHs, periplasmic extracts of the 91 LTΒR specific clones were tested for blocking of the LTβR:LIGHT interaction in ELISA. All 91 VHHs resulted in the reduction of LTΒR binding to coated human LIGHT, with percent inhibition ranging from 5.53% to 95.36%. Seventy-four showed at least 20% inhibition, and 33 showed at least 80% inhibition. Finally, the 91 clones selected after P.E. binding FACS results were screened on human isoform 1 and 2, cynomolgus monkey, and mouse LTβR-Fc proteins and other TNFRSF-Fc proteins (CD40, DcR3, and HVEM) directly immobilized on a CM5 sensor chip using the Biacore T200 for off rate (kd) determination. Off-rate values between 5.59 × 104and 8.55 × 102were observed with RU max > 35. Based on all screening assays, a lead panel of 20 VHHs was selected and cloned in pCB4 bacterial expression vector for large scale (250 mL) production. Periplasmic extracts containing soluble VHHs were purified via His tag using HisTrap HP 5 mL columns and desalting to 1 × PBS on HiTrap 5 mL OR columns in an ÄKTA pureTMsystem. The 20 purified VHHs were examined for QC by SDS PAGE, analytical SEC, and determination of melting temperature via DSC. Overall, between 1.04 mg and 4.62 mg of each anti-LTΒR purified VHH was obtained from production and purification. All purified VHHs examined for QC by SDS-PAGE ran with the expected molecular weight (15-20 kDa) under non-reducing conditions with high integrity and at least 93% monomeric VHH. However, FJ1828-VHH11H02 anti-LTΒR VHH showed a higher093699.0207 PATENT molecular weight band in the SDS-PAGE and 65% monomeric VHH. Concerning the DSC analysis, from the 20 anti-LTΒR purified VHHs characterized, 15 of them showed Tm> 65 °C. The 20 purified VHHs were further characterized for EC50value determination by binding ELISA on human, cynomolgus monkey, and mouse LTβR and other TNFRSF proteins, and binding FACS using human LTβR expressing and non-expressing cells. The EC50 values ranged between 3.30-47.45 nM and 0.91-23.99 nM on human LTβR isoform 1 and isoform 2 proteins, respectively, and between 0.66-27.17 nM on cynomolgus monkey LTβR Fc proteins. No binding was observed of the purified VHHs to the other TNFRSF proteins (CD40, DcR3, and HVEM), in agreement with the previous binding ELISA results observed during the screening phase as periplasmic extracts. From the binding FACS with the 20 purified anti LTβR VHHs, it was observed that 17 VHHs showed specific binding to HT29 cells, and none showed binding to NCIH1299 cells. The EC50values ranged between 1.17 nM and 26.44 nM on HT29 cells, although for some clones the EC50was estimated as no saturation was reached during the assay. The kinetic parameters and affinity values of the 20 anti-LTΒR purified VHHs to human, cyno, and mouse LTβR, and other TNFRSF proteins, directly immobilized on a CM5 chip at low density were determined in a Biacore T200. The KDvalues varied between 1.47 × 10-7M and 1.99 × 10-9M to human LTβR isoform 1 Fc protein, 1.46 × 10-8M and 1.97 × 10-9M on human LTβR isoform 2, and between 1.79 × 10-7M and 1.31 × 10-9M on cyno LTβR. None of the 20 purified VHHs showed association to the other TNFRSF proteins. The thermostability of the purified VHHs was also evaluated, VHHs were kept at 37 °C or 4 °C for 3 weeks and 6 weeks. After 3 and 6 weeks, the kinetic parameters were evaluated on human LTβR isoform 1 protein immobilized at low density in a CM5 sensor chip and compared to the profile of the VHH clones before the stress treatment. After 3 weeks at 4 °C, KDvalues (M) on human LTβR 1 Fc protein ranged between 1.07 × 10-7and 3.47 × 10-9and between 1.11 × 10-7and 3.87 × 10-9when stored at 37 °C. After 6 weeks at 4 °C, KD values (M) on human LTβR 1 Fc protein ranged between 1.06 × 10-7and 3.39 × 10-9and between 1.19 × 10-7and 3.68 × 10-9when stored at 37 °C. The kinetic parameters obtained before and after the different stress treatments were similar, indicating the high stability of the purified VHHs. Lastly, the agonistic activity of the 20 purified VHHs was evaluated in the soluble and immobilized approaches. Overall, higher activity was observed with the immobilization setup of anti-LTΒR VHHs via His tag, using an anti-His antibody, compared with no immobilization. The reporter assay was repeated, and, in both experiments, similar results were observed. At the highest concentration tested, 40 nM, the fold induction compared to the unstimulated cells ranged between 1.25 and 4.14 nM in the first assay and between 2.10 and 6.50 nM in the second assay. EC50 values093699.0207 PATENT ranged between 0.87 nM and 1.12 nM in the first assay and between 1.35 nM and 6.94 nM in the second assay. The NF-κB activation profiles obtained for the anti-LTβR VHHs were similar between both experiments. FJ1828VHH14D04 and FJ1828VHH14C03 showed the lowest EC50values in both experiments. The 20 anti LTβR purified VHHs were catalogued for further characterization. Example 2. Bispecific Antibody Production Bispecific antibodies (bsAbs) that target LTβR and a tumor-associated antigen (TAA) were evaluated in several formats to determine the optimal architectures (Figure 1 and Table 4). The parental variable regions (v-regions, VRs) used are described in U.S. Provisional Application No. 63 / 634,038. Heterodimeric antibodies were generated using knobs-into-holes mutations to enhance heterodimerization of the Fc subunits (Atwell, S., Ridgway, J. B., Wells, J. A. & Carter, P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol 270, 26-35, doi:10.1006 / jmbi.1997.1116 (1997); Ridgway, J. B., Presta, L. G. & Carter, P. 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 9, 617-621, doi:10.1093 / protein / 9.7.617 (1996)). In some cases, bsAbs also featured mutation of K248E and T437R (RE) to enhance cell surface-specific antibody clustering and LTβR agonism (Zhang, D. et al. Functional optimization of agonistic antibodies to OX40 receptor with novel Fc mutations to promote antibody multimerization. Mabs 9, 1129-1142, doi:10.1080 / 19420862.2017.1358838 (2017)). In some additional designs, the anti-LTβR v-region was formatted as either a single-chain fragment variable (scFv) or as a “stapled” single chain Fv (spFv). The VL-VH orientation spFv consists of a linker having a central “C1PPC2” motif [SEQ ID NO: 2474] wherein C1forms a disulfide bond with an engineered cysteine at position 43 (Chothia numbering) in the variable light domain and C2 forms a disulfide bond with an engineered cysteine at position 100 in the variable heavy domain (Table 2) (Chothia, C., & Lesk, A. M., 1987, J Mol Biol, 196:901-917). The VH-VL orientation spFv consists of a linker having a central “C1PPC2” motif wherein C1 forms a disulfide bond with an engineered cysteine at position 43 (Chothia numbering) in the variable heavy domain and C2 forms a disulfide bond with an engineered cysteine at position 100 in the variable light domain (Table 2). The staple design is meant to increase the thermal stability of the Fv domain and to limit aggregation during storage at high concentration and has no impact on activity. The sequences of the linkers are described in SEQ ID Nos:2457-2461. The sequences of the antigens are described in SEQ ID Nos: 2462-2469. The proper disulfide bonds form during expression of the molecule and no additional purification methods were used. Additionally, one potential challenge to use of spFv is transient interaction of the Fab VL with the spFv VH, followed by improper disulfide bond formation between these two093699.0207 PATENT chains. This was limited by use of the E9 variable region as spFv since it contained a lambda VL whereas the Fabs featured a kappa VL. The difference in LC isotype limited transient interactions between LC and spFv VH. The bsAbs were generated by co-expression of the heavy and light chains followed by first affinity purification using protein A and second step gel filtration of ion exchange chromatography. The activities of the molecules are described herein and comparisons across formats enable selection of a lead format for an anti-LTβR × anti-EDB bsAb that displayed LTβR agonism with similar activity to recombinant LIGHT. Antibodies were produced by transient expression in ExpiCHO cells according to the manufacturer’s protocol. The filtered cell culture supernatant was loaded onto a pre-equilibrated (1 × DPBS, pH 7.2) custom MabSelect PrismA ProA column (GE Healthcare, 2.6 cm × 10.7 cm, CV = 56.8 mL) at 20 mL / min using an AKTA Avant 25. After loading, the column was washed with 1 × DPBS, pH 7.2 until the UV signal stabilized near baseline. The protein was eluted with 0.1 M Acetate, pH 3.4, and the eluate was neutralized in-line by the addition of 2.5 M Tris HCl, pH 7.5 to approximately 12.5% (v / v) total volume and filtered (0.2 µm). Post-ProA capture material was diluted with 20 mM MES, pH 5.5 and allowed to sit at room temperature for at least 1 hour to precipitate any non-target substances in solution. The sample was then 0.2 µm filtered and polished by CEX using a custom Capto S ImpAct column (GE Healthcare, 2.6 cm × 36.4 cm, CV = 193 mL) on an AKTA Avant 25. The protein was loaded at 15 mL / min and then eluted from the column with an increasing NaCl gradient at 10 mL / min (100-213 mM over 5.9 CVs and then 213-1000 mM over 0.5 CV) in 20 mM MES, pH 6.5. The peak fractions containing only monomeric protein were pooled, 0.2 µm filtered, dialyzed into 10 mM Histidine, pH 6.5 and 0.2 µm filtered again. Proteins were purified to > 95% purity for functional analyses. Example 3. Binding data (SPR) Binding was measured for both human LIGHT and the anti-LTβR E9 v-region to human and mouse LTβR. Human LIGHT was featured as a C-terminal fusion to the anti-MSLN Ab LTΒRB99 while the anti-LTβR E9 v-region was featured as a C-terminal fusion to the anti-MSLN Ab LTΒRB90. Both fusion proteins featured a mouse Fc region. Surface plasmon resonance (SPR)-based binding analysis was carried out using a Biacore 8K using the included manufacturer’s software (Cytiva). Binding to mouse LTβR (LTΒRW5, LTβR-mouse Fc, R&D systems cat. # 1008-LR) was carried out by amine coupling of the ligand onto the chip and titrating the antibodies. Binding to human LTβR (LTΒRW2, LTβR-human Fc, R&D systems cat. # 629- LR) was carried out using either amine coupling of the ligand or via goat-anti-human Fc capture of the antigen and titrating the antibodies. Antibody binding was analyzed at concentrations of 300,093699.0207 PATENT 100, 33, 11, and 3.7 nM and binding was assessed using single-cycle kinetics mode and processed using a 1:1 Langmuir model. Both LTΒRB90 and LTΒRB99 bound human LTβR more tightly than mouse LTΒR. Binding to human and mouse MSLN was evaluated using LTRB90 and LTΒR99, respectively since both constructs contain the same MSLN binding Fab arm. Human LIGHT bound to human LTβR with equilibrium dissociation constant (KD) of 70.3 pM and bound to mouse LTβR (Table 7). The anti-LTβR E9 scFv bound to human LTβR with KD of 193 pM and bound to mouse LTβR with KD of 3.83 nM. Although binding to mouse LTβR was observed, binding parameters were not quantitated due to poor fit of the data. Example 4. Variable Region Fitness Analysis The v-region (VR) sequence of the anti-LTβR E9 v-region was analyzed for risks of potential post-translational modifications, for germline fitness, and for their abilities to format as scFv. The anti-LTβR v-region, named clone E9 (VR000051222) was discovered by immunization of humanized chickens (Ligand Therapeutics) and featured the human heavy chain germline IGHV3-23*01-IGHJ6*01 and the light chain germline IGHV3-23*01-IGHJ1*01 (Lorenzi, M. L., et al., WO2021 / 116337A1). The v-region displayed no significant risks for post-translational modification or immunogenicity risk based on in silico analysis using the EpiVax Epimatrix in silico immunogenicity prediction program (De Groot, A. S. & Martin, W., 2009, Clinical Immunology, 131:189-201). The anti-LTβR E9 v-region was also evaluated for thermal stability in scFv format. Briefly, the v-region was cloned into scFv format in both the VH-linker-VL or the VL-linker-VH orientations and expressed in E. coli. The culture supernatants were assessed by ELISA for their abilities to bind recombinant LTβR (Figure 2, Table 8). Supernatant samples were also heat treated at either 55, 60, or 65 °C, and the binding of the heat-treated samples was compared to the unheated samples after re-equilibration at room temperature. This analysis provided an estimate of the thermal stability of the v-region when formatted as scFv. The E9 v- region was able to maintain > 95% of binding compared to the unheated sample even after heat treatment at 65 °C. Together, these results suggested that the anti-LTβR E9 v-region had favorable properties for therapeutic development. Example 5. Epitope Mapping Hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine whether the anti-LTβR E9 v-region bound to a similar epitope on LTβR as its endogenous ligands LTα1β2 and LIGHT. The extracellular domain of LTβR is comprised of four cysteine rich domains (CRDs), and the crystal structure of LTβR bound to Lta1 (PDB ID 4MXW) showed that, similar to other093699.0207 PATENT TNF-TNFR interactions, LTα1β2 bound primarily to the membrane distal CRD1 and CRD2 (Sudhamsu, J. et al. Dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction. Proc Natl Acad Sci U S A 110, 19896-19901, doi:10.1073 / pnas.1310838110 (2013)). Based on the similarity between LTα1β2 and LIGHT, and the observation the most TNF ligands bind to the two membrane distal CRDs, a model was generated for the interaction between LTβR and LIGHT by first docking the crystal structure of LIGHT bound to DcR3 (PDB ID 4J6G) onto that of LTα1β2 and then applying 3-fold symmetry (Figure 3A) (Liu, W. et al. Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly. Structure 22, 1252-1262, doi:10.1016 / j.str.2014.06.013 (2014)). Using HDX it was confirmed that the residues in LTβR whose H-D exchange rate changed upon binding LIGHT were consistent with this model (Figure 3B). It was demonstrated that the epitope on LTβR bound by the E9 v-region largely overlapped that of LIGHT, suggesting that the two binders would compete and that the E9 v-region could potentially mediate LTβR activation and downstream signaling, similar to LIGHT (Figure 3C). The sequence alignment of LTβR from human, cynomolgus monkey, rat, and mouse shows that the ECD displays 96, 67, and 69% identity while the epitopes for E9 are 98, 71, and 71% identical and for LIGHT are 98, 70, and 70% identical, respectively (Figure 4, Table 9). Example 6. EDB epitope analysis The anti-fibronectin L19 v-region was reported to interact specifically with the extra domain B domain (ED-B) (Pini, A. et al. Design and use of a phage display library. Human antibodies with subnanomolar affinity against a marker of angiogenesis eluted from a two- dimensional gel. J Biol Chem 273, 21769-21776, doi:10.1074 / jbc.273.34.21769 (1998)). The ED- B-containing fibronectin variant is an oncofetal marker – displaying limited expression in normal adult tissue but high upregulation during embryogenesis and in some solid tumors – making it an attractive therapeutic target (White, E. S. & Muro, A. F. Fibronectin splice variants: understanding their multiple roles in health and disease using engineered mouse models. IUBMB Life 63, 538- 546, doi:10.1002 / iub.493 (2011); Lieverse, R. I. Y. et al. Human fibronectin extra domain B as a biomarker for targeted therapy in cancer. Mol Oncol 14, 1555-1568, doi:10.1002 / 1878-0261.12705 (2020); Castellani, P. et al. The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. Int J Cancer 59, 612-618, doi:10.1002 / ijc.2910590507 (1994)). Indeed, a bi-functional L19-TNF immunocytokine showed a favorable safety profile and efficacy in clinical evaluation (Papadia, F. et al. Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. J Surg Oncol 107, 173-179, doi:10.1002 / jso.23168 (2013)).093699.0207 PATENT Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to confirm that the L19 v- region binds only to the ED-B domain. H-D exchange rates of a construct comprised of the FNIII domain 7-ED-B-FNIII domain 8 of fibronectin were measured in the absence or presence of LTΒRB509, a bsAb that features the anti-EDB L19 v-region. Residues 1304-1314 and 1318-1322 (all within the ED-B) showed changes in H-D exchange rate and represented the binding epitope for the L19 v-region exclusively on ED-B (Figure 5A and Figure 5B). This result suggested that the binding mode of the L19 v-region was specific to ED-B and that it would thus display limited on-target toxicity when dosed in mammals. The sequence alignment of the ED-B domain from human, cynomolgus monkey, rat, and mouse shows 100% identity, suggesting the rodents or non- human primates could be used to evaluate safety of the molecules (Figure 6, Table 10). Example 7. Cell Binding of Bispecific Antibodies with Different Architecture Test samples and controls were prepared at 120 nM in stain buffer. Seven-fold serial dilutions for a 6-point titration of compounds in polypropylene plates were prepared. Additional wells were used for other controls in stain buffer. VcaP, NCI-H292, NCI-H292 LTΒR KO, NCI- H1048, NCI-H596, HCC827, NCI-H1703, NCI-H82, A2780, and HGC-27 cells were used. Cells were harvested from the cell culture flasks using cell dissociation buffer, 100 µm strained and then diluted to ~1 × 106cells / ml and plated in 50 µL stain buffer (BD# 554657) for 50,000 cells / well into a V-bottom tissue culture treated polystyrene assay plate. Assay plates were prepared with 50 µL / well of serially diluted antibodies or controls. Plates were incubated at 4 °C for 1 h. Following the incubation 100 µL of staining buffer was added per well and assay plates were centrifuged at 300 × g for 5 min and buffer was removed from the wells. 200 µL staining buffer was added to each well and the plates were centrifuged at 300 × g for 5 min and buffer was removed from the wells.50 µL of 2 µg / ml AF647 labelled goat anti-human secondary polyclonal Ab in stain buffer was added and plates were incubated for 30 min at 4 °C. Following the incubation 150 µL of staining buffer was added per well and assay plates were centrifuged at 300 × g for 5 min and buffer was removed from the wells. 200µL running buffer (staining buffer with 0.1% Pluronic acid, 1 mM EDTA) was added to each well and the plates were centrifuged at 300 × g for 5 min and buffer was removed from the wells.30 µl of running buffer with 1 µM Sytox blue was added (1:1000 of 1mM stock). The cultures were assessed using flow cytometry on the Intellicyt IQ Plus or IQ3 for viable tumor cells using Sytox blue live / dead stain, and also gated on singlets. Data for RL1H signal divided by secondary only control wells was plotted vs. antibody concentration in Gene Data Screener using 4 parameter curve fitting to generate EC50and Bmaxvalues. To assess the specificity of binding by the bsAbs, we evaluated a panel of antibodies for their abilities to bind cells that expressed either the tumor targets alone, LTβR alone, or one or093699.0207 PATENT more tumor targets in addition to LTβR (Tables 12-14, Figure 19). The mean fluorescence index (MFI) and binding EC50values were compared. Higher MFI and tighter EC50indicate stronger binding, which can be driven by either antibody affinity, valency, or receptor density. bsAbs that targeted MSLN or EGFR were evaluated with or without binding to LTβR via either the E9 v- region or scLIGHT. The molecules featured different formats (Table 1). Most bsAbs displayed specific binding to cells expressing their targets. One format, exemplified by LTΒRB11, LTΒRB12, LTΒRB21, and LTΒRB15 having the anti-LTβR E9 v-region formatted as an N- terminal scFv on one subunit of the Fc paired with a tumor targeting arm formatted as a Fab on the other arm, failed to show binding or in some cases showed modest non-specific binding, suggesting that the E9 v-region may not have folded correctly in this format where its N-terminus was free or that N-terminal LTβR binding domains were not active, leading to unexpected binding results. Similar lack of binding or modest non-specific binding was observed in analogous formatted molecules differing only in that the anti-LTβR E9 v-region was replaced with a trimeric scLIGHT moiety on the N-terminus of heavy chain 1 (Figure 1K). This format was exemplified by LTΒRB16, LTΒRB17, and LTΒRB20 (Table 4). The overall lack of binding to LTβR-expressing cells by these molecules supported the observation that an N-terminal LTβR binding domain was less optimal. Next, bsAbs having two anti-TAA Fab domains and a single LTβR binding domain were examined. These were formatted either with the anti-LTβR E9 v-region “wedged between the Fab and Fc of heavy chain 1 (LTΒRB34, LTΒRB35, LTΒRB36, LTΒRB37, LTΒRB38, LTΒRB39, LTΒRB40, LTΒRB41, LTΒRB42, and LTΒRB43, Figure 1L) or in a “Morrison-type” format in which the LTβR binding domain was fused to the C-terminus of the Fc on one of the heavy chains (Coloma, M. J. & Morrison, S. L. Design and production of novel tetravalent bispecific antibodies. Nat Biotechnol 15, 159-163, doi:10.1038 / nbt0297-159 (1997)). This format was exemplified by LTΒRB44, LTΒRB45, LTΒRB24, LTΒRB25, LTΒRB26, LTΒRB6, LTΒRB7, LTΒRB8, and LTΒRB9 (Figure 1B). These molecules mostly bound as expected, with few exceptions. LTΒRB43, a null control displayed some non-specific cell binding to HCC827 cells. All of the Morrison-type antibodies displayed specific binding to only those cell types expressing target, suggesting that this format was more optimal for bispecific targeting of TAAs and LTβR. In summary, use of the anti-LTβR E9 v-region generally resulted in antibodies that specifically bound target-expressing cells compared to use of scLIGHT fusions, and antibodies having the Morrison-type format, in which the anti-LTβR E9 v-region was fused to the C-terminus of the Fc, displayed more optimal binding properties compared to N-terminal fusions.093699.0207 PATENT Example 8. Cell Binding of Bivalent LTβR Bispecific Antibodies Since C-terminal fusions of the anti-LTβR E9 v-region demonstrated improved binding than N-terminal fusions, it was next examined whether changing the valency of either the TAA binding region or the LTβR binding region could interfere with or enhance cell binding. The ability of a panel of antibodies to specifically bind cells that express either MSLN only (HGC27), LTβR only (MCF7, CT26.WT) or both MSLN and LTβR (huMSLN-CT26) was examined. As CT26 cells expressed only mouse LTβR, a CT26 cell line was engineered to express human MSLN (Table 8). bsAbs were evaluated as having 0, 1, or 2 binding domains for either MSLN and LTβR (Table 4) to confirm (a) that the binding domains were specific for their targets and (b) whether bi-valency would confer additional binding benefit via avidity. Cells were collected using Enzyme-free dissociation buffer (Gibco, 12151-014), and transferred (1-3 × 105cells / well) in low attachment 96-wells U-bottom plate (Costar, Cat. No. 7007), centrifuged at 400 × g for 4 min, and washed with 150 ml of PBS. Cells were stained with Near-IR live / dead stain (Thermofisher, Cat. No. L34976) according to manufacturer’s protocol. Cells were washed with PBS as described above and thereafter incubated at room temperature for 10-15 min with Human Fc block (BD564220; 0.5 mg / ml, 2.5 mg / well). Afterwards, the plate was centrifuged at 400 × g for 4 min and the supernatant discarded. Respective test antibodies (or corresponding silent Fc huIgG1 kappa), diluted to appropriate concentrations (final concentration range 70 nM – 0.032 nM; 3-fold dilution steps) in FACS staining buffer, were added to the cells and incubated for 35-45 min at 4 °C. Cells were washed twice with the FACS staining buffer, followed by additional 35-45 min incubation with PE-labeled goat anti-human secondary Ab (Jackson Immuno, Cat. No.109-546-088) and final wash, before the analysis on FACS Fortessa. The data were analyzed with FlowJo v10. As expected, antibodies featuring a negative control α-RSV Fab (LTΒRB9 and LTΒRB387) did not show any binding to HGC27 cells. Antibodies that featured the α-MSLN Fab all bound HGC27 and CT26-huMSLN cells (LTΒRB44, LTΒRB145, and LTΒRB305, Figure 7). Monovalent MSLN binding bsAb LTΒRB305 showed higher maximal binding (Geomean values), in line with the ability of more monovalent antibodies to bind per cell. When tested for their abilities to bind MCF7 and CT26 cells that express only human and mouse LTβR, respectively, LTΒRB9, LTΒRB145, LTΒRB305, and LTΒRB387 all displayed similar levels of binding. On CT26-huMSLN cells that expressed both targets, LTBRB305 showed improved binding, while LTBRB387 and LTBRB9 displayed comparable binding. EC50values for binding are reported in Table 14.093699.0207 PATENT Example 9. NK-kB Activation by LTβR Bispecific Antibodies The abilities of the antibodies to activate LTβR signaling were next examined using an NF- κB reporter cell line (Figure 8A through Figure 8B, Table 15). The NF-κB reporter plasmid that was used to generate the cell line contains the canonical NF-κB binding site “GGGAATTTCC” (SEQ ID NO: 2471) in the promoter region. Therefore, the canonical (NEMO / IKK dependent) NF- κB activation can be directed towards luciferase gene expression. Two reporter cell lines- A549 lung epithelial NF-κB-luc reporter cell line (BPS Bioscience, Cat. No.60625) and NIH-3T3 murine fibroblast NF-κB-luc reporter cell line were used to assess the bsAb functional activity. For testing of the MSLN × LTβR bsAbs, a co-culture of the reporter cell lines with MSLN expressing cell lines were made. A549 NF-κB-luc reporter cells were plated in culture with NCI- H596 human lung adenosquamous carcinoma cells (ATCC HTB-178). To support the use of the LTβR E9 v-regions in murine in vivo models, it was also confirmed that the NF-κB induction occurred using a murine NIH-3T3 NF-κB-luc reporter cell line. NIH / 3T3 NF-κB-luc reporter cells were co-cultured with human MSLN expressing mouse pancreatic ductal adenocarcinoma CT26 cells (CT26-huMSLN). For co-culture experiments, the MSLN expressing cells (NCI-H596 or CT26-hMSLN) were plated at 2 × 105cells / well in 100 ml of medium and allowed to attach for approximately 6 hours. Afterwards, 2 × 105NF-κB-luc reporter cells / well (either A549 or NIH- 3T3) in 50 ml of medium were added for a 1:1 cell ratio, and bsAbs were added for final volume of 200 ml, and cells incubated 18 hours at 37 °C and 5% CO2. For testing of the EDB × LTβR bsAbs, plates (96-well, NUNC Maxisorp plates, VWR, Cat. No. 735-0097) were precoated with 50 ml of huFN-7-EDB-8-9 recombinant protein at a concentration of 3 µg / ml (corresponding to 150 ng / well) and incubated overnight at 4 °C. Afterwards, coating solution was removed and wells were washed twice with 120 ml of PBS and thereafter blocked with 120 µl of assay medium for 2 hours at 37 °C. Cells (20,000 cells / well) were added to each well, followed by addition of test antibodies at different concentrations. Cells were left treated for 18 hours at 37 °C and 5% CO2. After incubation, Bio-GloTMreagent (Bio-GloTMLuciferase Assay System; Promega, Cat. No. G7941) was prepared according to manufacturer’s instruction, added to the wells, and incubated at room temperature for 10 min in the dark with constant shaking (600 rpm). Cell suspension (160 µl) was then transferred to white non-binding plates (OptiPlate-96, White Opaque 96-well Microplate; Perkin Elmer, Cat. No. 6005290) and luminescence signal was analyzed on the Envision machine (integration time 500 ms). NF-κB activation was calculated as fold induction093699.0207 PATENT compared to the control condition by dividing relative light units (RLU) of treated cells) with RLU of non-treated cells. NF-κB signaling triggered by LTβR activation with LTβR-monovalent bsAb (LTBRB383) was further enhanced by LTβR-bivalent bsAbs (LTBRB145 and LTBRB305)(Figure 8 and Figure 9). Activation of NF-κB signaling was driven by simultaneous binding to cells expressing MSLN and to the LTβR-NF-κB-luc reporter cells, since LTΒRB387 and LTBRB381, which could only bind LTβR, displayed weaker activation (Figure 8A and Figure 9) than the bsAbs that could bind MSLN (LTΒRB145, LTBRB305 and LTΒRB383) and the activation was very reduced or abrogated in the absence of MSLN-expressing cells (Figure 8B and Figure 9). NF-κB induction was enhanced in the presence of MSLN-expressing cells for the bsAbs that could bind MSLN and LTβR, whereas the control α-RSV × LTβR bsAbs showed no enhancement of NF-κB signaling by the presence of MSLN-expressing cells. While the antibodies with two copies of the E9 v-region could induce some signaling in the absence of tumor-target-expressing cells, the activation was much less pronounced, in particularly for LTBRB145 compared to LTBRB305 (Figure 8A compared with Figure 8B; Table 15). The observation that binding to the tumor target is required and / or enhances the ability of the tumor-associated antigen (TAA) × LTβR bsAbs to induce NF- κB signaling, reveals that clustering of LTβR agonism is important for maximum signal induction. The magnitude of LTβR agonism using the anti-LTβR E9 v-region was ~ 75% that of the endogenous ligands, likely because the ligands are capable of binding two or three subunits of LTβR, whereas the E9 v-region can only bind one subunit. However, the observation that a single anti-LTβR E9 v-region could mediate LTβR agonism only when formatted as part of the MSLN × LTβR bsAb, and not α-RSV × LTβR, suggests that LTβR may be cross-linked to an extent by simultaneous binding to the TAA, such that binding only one subunit can induce downstream signaling to a modest extent. Overall, results were consistent in that (a) TAA binding granted and enhanced NF-κB signaling induction and (b) bivalent binding to LTβR by the anti-LTβR E9 v- region led to further enhanced signal induction (LTΒRB145 vs LTΒRB383). EC50values were somewhat lower in the human reporter cell line, consistent with higher affinity of E9 binding arm for human compared to murine LTβR and murine reporter lines. Since Fc modifications that enhance target cell-specific clustering can enhance agonistic activity, particularly for some TNFRSF members, it was evaluated whether use of the K248E and T437R (RE) mutations could enhance the agonistic activity of the membrane TAA-targeting anti- LTβR bsAbs (Figure 10) in inducing the NF-κB signaling activation. A panel of antibodies which could bind both MSLN and LTβR as mono-valent or bi-valent binders were designed with either the silent IgG1 or silent IgG1 RE format. In some cases, particularly wherein the C-terminal anti-093699.0207 PATENT LTβR v-region was monovalent, use of the RE mutations for clustering resulted in modestly enhanced activity (Figure 10A). The effectiveness of Fc-clustering depends on the density of antigen present on the target cells, and thus, whereas clustering-based enhancements may be modest against some targets or cell lines, the effects may be more prominent in other bsAb designs. In one example, a bsAb that was bivalent for binding both MSLN and LTβR (LTΒRB145) showed ~ 20% enhanced activity when fitted with the RE-based Fc mutations (LTΒRB148) (Figure 10B). Analogous experiments were performed using the human A549 NF-κB luciferase reporter cell line with EDB L19 × LTβR E9 bsAbs to assess whether (a) tumor target engagement-based clustering could grant and enhance LTβR agonism in the context of an extracellular matrix target and (b) whether bivalent binding to LTβR would enhance activity. In this assay, recombinant Fn- 7-EDB-8-9 was used to coat the assay plates. First, antibodies that featured the EDB L19 Fab or a α-RSV Fab and either a single copy of the anti-LTβR E9 v-region (LTΒRB384 and LTΒRB381) or two copies of the anti-LTβR E9 v-region (LTΒRB146 and LTΒRB387) were examined for their abilities to activate NF-κB signaling (Figure 11, Table 16). In this evaluation, the antibodies that engaged EDB could .induce NF-κB signaling. This activity could be achieved at much lower concentrations in case of bivalent binding to LTβR, since the bivalent LTβR-binding LTΒRB146 showed ~ 20-fold reduced EC50 compared to its monovalent counterpart LTΒRB384 (Figure 11A, Table 16). Next, it was examined how the agonism of the anti-LTβR E9 v-region compares to ligand-induced signaling by generating fusion molecules in which the E9 v-region was replaced with a single copy of the single-chain (sc) LIGHT trimer (Figure 11B). Although NF-κB signaling was enhanced by EDB binding, exemplified by the enhanced luciferase activity of LTΒRB162 (α- EDB × LIGHT) compared to LTΒRB29 (α-RSV × LIGHT), in contrast to α-RSV × single copy of the LTβR E9 v-region (LTΒRB381), TAA binding of LIGHT-containing molecules was not required for agonism and LTBRB29 demonstrated significant dose dependent NF-κB signaling. This suggested that use of the anti-LTβR E9 v-region may confer a therapeutic advantage since its inability to induce LTβR agonism in the absence of TAA may limit systemic activation and associated toxicity. Next, the time-course of NF-κB induction was assessed using bsAbs that bound EDB and LTβR, as well as α-EDB × LIGHT and α-EDB × LTα1b2 fusion proteins (Figure 12). In all bsAbs evaluated, NF-κB signaling was significantly induced only after 4 hours, and induction levels were similar between 4 and 6 hours. Comparison of EDB-bivalent × LTβR-monovalent (LTΒRB384) and EDB-bivalent × LTβR-bivalent (LTΒRB146) bsAbs revealed that bivalent LTβR binding resulted in lower EC50and increased maximum signaling induction at lower concentrations at 4 and 6 hours (Figure 12). Fusion proteins that featured a single LIGHT (LTΒRB162) or single093699.0207 PATENT LTα1b2 (LTΒRB137) displayed similar EC50 and maximum induction values at 6 hours as EDB- bivalent × LTβR-bivalent (LTΒRB146) bsAb (Figure 12), suggesting that this format would be amenable to similar activity as endogenous ligands. Example 10: Non-canonical NF-κB Activation by Mono- and Bi-valent LTβR bsAbs. The NF-κB family is composed of five related transcription factors that form homo- and heterodimeric complexes including NF-κB1 (p50 and its precursor p105), NF-κB2 (p52 and its precursor p100), RelA (p65), RelB, and Rel (c-Rel). NF-κB activity is tightly controlled by a collection of inhibitory proteins that belong to the IkB family, which include IkBα, IkBb, IkBe, Bcl-3, p100, and p105. LTβR ligation leads to activation of IkBb and RelA (canonical pathway), which control the expression of inflammatory genes such as VCAM-1, MIP-1b, and MIP-2. In addition, this pathway leads to an increase of NF-κB2 / p100 precursor. The processing of the latter is controlled by a second pathway (non-canonical pathway) regulated by the IKK1 (IKKα) subunit of the IKK complex that involves the activation of NIK which in turn activates IkBα for generating active p52. P52 in association with its partners (e.g., RelB) translocates to the nucleus and activates the transcription of genes implicated in secondary lymphoid organogenesis and homeostasis such as SLC, ELC, BLC, SDF-1α, and BAFF. Only a small number of stimuli are known to activate NF-κB via a non-canonical pathway, among these is LTβR. The effect of LTβR ligation on the activation of canonical and non-canonical pathways was examined using EDB-binding LTβR-agonistic antibodies LTBRB384 and LTΒRB146 (or LTBRB509) and fusion proteins LTΒRB162 (LIGHT) and LTBRB137 (LTα1b2), and TNF-α as a cytokine stimulating canonical, but not non-canonical pathway. LTΒRB146 and LTΒRB162 induced degradation of p100 starting from 2 hours post treatment, indicating activation of non- canonical NF-κB pathway, while TNF-α did not reduce the p100 levels. 6-well plates were pre-coated with Fn-7-EDB-8-9 recombinant protein in carbonate- bicarbonate buffer at a concentration of 3 µg / ml (corresponding to 150 ng / well) and incubated overnight at 4 °C. Wells were washed twice with PBS and blocked with assay medium for 2 hours at 37 °C. A549 NF-κB reporter cells (6 × 105cells / well) were added to the huFN-7-EDB-8-9 coated plates and were left unstimulated or treated with 20 ng / ml of TNF-α or LTΒRB146 and LTΒRB162 at 10 mM for 20 min, 1 hours, 2 hours, 4 hours, 6 hours and 24 hours. In a separate experiment A549 NF-κB reporter cells (6 × 105cells / well) were added to the huFN-7-EDB-8-9 coated plates and were left unstimulated or treated with dose range of TNF-α or EDB-binding LTβR-agonistic antibodies LTBRB384 and LTΒRB509 or fusion proteins LTΒRB162 (LIGHT) or LTBRB137 (LTα1b2) for 4 hours. After the indicated time points, the plates were briefly centrifuged (400 × g, 4 min), wells were washed twice with PBS and the plate stored at -80 °C for the subsequent093699.0207 PATENT analysis. Lysates of the cells were prepared upon thawing of plates on ice in Mper lysis buffer with 1 × protease / phosphatase inhibitor and Benzonase (80 ml per 6-well). Plates were incubated for 20 min at 4 °C, afterwards wells were scraped and collected lysate centrifuged at 13,000 rpm for 15 min at 4 °C. Protein content was determined using Pierce 660 nm Protein Assay reagent according to manufacturer’s instructions and supernatants kept at -80 °C until analysis by Jess protein analysis. Samples were analyzed by Jess using the following antibodies for detection: NF-κB2 p100 / p52 Antibody (Cell Signaling, #4882) was used for detection of p100 and p52 proteins, respectively. Phospho-NF-κB p65 (Ser536) (93H1) rabbit mAb (Cell Signaling, #3033) was used for detection of phosphorylated p65 and NF-κB p65 (L8F6) mouse mAb for detection of total p65 protein. Phospho-IkB-alpha (Genetex, GTX00967) was used for detection of phosphorylated IkBα. Levels were normalized against total protein using Jess protein normalization module (DM-PN02). LTβR signaling triggered by LTΒRB146 and LTΒRB162 induced degradation of p100 and generation of p52, evident by induction in p52 / p100 ratio, starting from 2 hours post treatment and spiking at 4-6 hours post activation, indicating activation of non-canonical NF-κB pathway. In line with specific activation of canonical NF-κB pathway by TNF-α, TNF-α did not change p52 / p100 ratio (Figure 13). Interestingly, LTβR-monovalent (LTBRB384) bsAb induced the canonical pathway to a modest degree, detected by induction of phospho-p65 and phospho-IkBα, but failed to induce the non-canonical NF-κB pathway (Figure 13). In contrast, LTβR-bivalent (LTΒRB146) bsAb and endogenous ligand LIGHT (LTΒRB162) or LTα1b2 (LTΒRB137) fusion proteins displayed dose dependent and pronounced activation of both, canonical and non-canonical NF-κB pathways (Figure 14). These data highlight the requirement of LTβR clustering in non- canonical NF-κB pathway activation. Example 11: Induction of cytokines by Mono- and Bi-valent LTβR bsAbs Next, it was assessed whether the EDB-dependence of NF-κB induction would likewise result in a similar EDB-dependence on chemokine production. For this, an MSD-based assay was used, in which culture supernatants were assessed for the presence of the inflammatory cytokines and chemokines produced as a result of LTβR-signaling (Lau, T. S., et al., 2014, J Pathol, 232:43- 56; Mikami, Y., et al., 2014, PloS One, 9:e114791; Hehlgans, T., et al., 2003, Eur Cytokine Netw, 14(2):103-107). Plates had either immobilized Fn-7-EDB-8-9 recombinant protein or were blocked without pre-coating as negative controls. bsAbs were evaluated in three formats. All bsAbs featured bivalent binding to either EDB (or RSV control) and one or two copies of the anti-LTβR E9 v-region or a single scLIGHT moiety. NUNC high binding 96-well plates were pre-coated with Fn-7-EDB-8-9 recombinant protein in carbonate-bicarbonate buffer at a concentration of 3 µg / ml (corresponding to093699.0207 PATENT 150 ng / well) and incubated overnight at 4 °C. Wells were washed twice with PBS and blocked with assay medium for 2 hours at 37 °C. NCI-H596 cells (5,000 per well) were added and incubated overnight for cells to attach. Afterwards, the medium was replaced with fresh medium containing the antibodies (max. final concentration 50 nM and 4-fold dilution for total of 10 concentrations) and the cells were incubated for an additional 72 hours. Recombinant LIGHT (MW 20.9Da) was used as a positive control. The supernatants (100 ml) were harvested, centrifuged at 500 × g for 5 min and 80 ml of cell-free supernatants were transferred into low attachment plate and stored at - 80 °C until the analysis. An MSD U-PLEX Biomarker Group 1 (hu) Assay kit was used to determine human IL-6, IL-8, IP-10, I-TAC and IL-12 / 23-p40 according to manufacturer’s protocol and analyzed with methodical mind software. Cytokine production was significantly enhanced in the presence of α-LTβR bsAbs or LIGHT fusion proteins (Figure 15A through Figure 15C). The observation that the homodimeric Morrison-type antibody, LTΒRB146, that could bind both EDB and LTβR resulted in identical levels of chemokine production to the EDB-binding LIGHT fusion protein (LTBRB162), suggests that this format may present an alternative activation of LTβR and that LTβR agonism in this format might be enhanced by clustering on tumor cells. This observation was also corroborated by the observation that antibodies whose Fab regions had α-RSV v-regions (LTΒRB387, LTBRB381, and LTΒRB29) induced only low levels of chemokine production compared to their counterparts that could bind EDB (LTΒRB146, LTΒRB384, and LTΒRB164, respectively) Example 12: Induction of Monocyte Transmigration through Endothelial Monolayer by Mono- and Bi-valent LTβR bsAbs Monocytes were purified from EDTA-blood collected from healthy donors using a negative selection kit (Miltenyi Biotec #130-96-537) and used at 1.5 × 106cells / ml. HUVEC cells were cultured in microscope flow chamber slides for 2-3 days using predefined coculture coating conditions of FN-7-EDB-8-9 recombinant protein. The 1-day stimulation was conducted after achieving confluence (attained after 2-days seeding) with control recombinant LIGHT (50 nM) and experimental groups (each EDB × LTβR bsAb at 50 – 10 – 2 – 0.5 – 0.08 – 0.015 – 0.0025 – 0.0005 nM concentrations). The flow assay set-up consisted of a heated microscope chamber (37 °C) and a calibrated pump where flow could be generated over HUVEC monolayers by perfusing wash buffer (culture media, 0.1% BSA) + / - leukocyte suspension. The flow rate is representative of small venules / capillaries (0.05 Pa). Wash-buffer was then pumped over the HUVECs for 10 minutes to remove the activation media. Monocytes were then perfused over the HUVECs for 6 minutes followed by 50 minutes of wash-buffer. Throughout the 50 minute wash093699.0207 PATENT period, images of the captured monocyte were made using phase-contrast microscopy and an attached camera. The total number of adherent cells is representative of the sum of captured cells at each time point; a percentage of which transmigrated. Transmigration events are a percentage of total leukocytes captured from flow per unit field. All experiments were carried out using triplicate fields and presented as a mean value with + standard error measurements (+SEM). Statistical analyses assume parametric distributions and were conducted using the Student T test. In line with the NF-κB signaling pathway activation and induced cytokine production, EDB-bivalent × LTβR-monovalent (LTΒRB384) and EDB-bivalent × LTβR-bivalent (LTΒRB146) bsAbs induced monocyte transmigration in time- and dose-dependent manner, where the bivalent LTβR binding resulted in comparable EC50 and increased maximum signaling induction at lower concentrations (Figure 16). Fusion protein that featured a single LIGHT (LTΒRB162) displayed similar EC50and maximum induction values as EDB-bivalent × LTβR- bivalent (LTΒRB146) bsAb (Figure 17, Table 17). Example 13: In vivo efficacy BsAbs were tested for their abilities to mediate anti-tumor efficacy in vivo in a series of mouse studies in syngeneic cell line derived xenograft (CDX) models (parental) CT26 and human MSLN (hMSLN) and EGFR (hEGFR) transgenic CT26 and MC38 cell lines). E9-bsAbs and LIGHT fusion proteins targeting either MSLN (CT26-hMSLN and MC38-hMSLN CDX), EGFR (CT26-hEGFR) or EDB (parental CT26 CDX) were assessed for tumor growth inhibition and / or improved life span (ILS), alone or in combination with anti-PD-1 in established syngeneic mouse models. The initial study consisted of an efficacy experiment with the murine colon carcinoma cell line implanted subcutaneously (1 × 105cells / mouse) in Balb / c mice. The experiment comprised seven groups of 10 mice each bearing a single CT26-hMSLN tumor. On day 11, at tumor volumes of 50 mm³ to 70 mm³, mice were distributed among the groups, aiming at comparable group mean and median tumor volumes. Two MSLN-redirecting bsAbs were evaluated at three dose levels. Antitumor efficacy of all groups was assessed using the vehicle control group as a reference. Treatment started on the day of randomization and was performed for total of 6 doses (intraperitoneally, twice per week). Tumor growth inhibition was determined at the end of the treatment period by the comparison of changes in tumor volumes of the test groups relative to changes in the PBS treated control group and was expressed as the delta TGI value (denoted TGI in text) in percent. This was day 21 post tumor implantation. Mice were further followed for survival and euthanized at tumor volume >1000 mm3. P-values were results of the semi-parametric Cox proportional hazard (PH) model from Kaplan Meirer Plot and were corrected for multiple093699.0207 PATENT comparisons using the false discovery rate method. The experiment was terminated on day 35. Treatment with 5 mg / kg LTΒRB99 (α-MSLN × LIGHT) resulted in significant tumor growth inhibition of 67.8% (p<0.0001), while 5 mg / kg LTΒRB99, 1 mg / kg LTΒRB90 and 5 mg / kg LTΒRB90 (MSLN × LTβR) resulted in a trend of CT26-hMSLN tumor growth inhibition in Balb / c mice (49.4%, p = 0.003; 36%, p = 0.0006 and 41.5%, p = 0.0007, respectively; Table 18). Similar results were obtained in efficacy assessment of LTΒRB88 (EDB × LTβR) and LTΒRB97 (α-EDB × LIGHT) in subcutaneous CT-26 (parental) model (0.5 × 106) in Balb / c mouse. Animals were randomized into groups by tumor volume (~50-100 mm3) on day 7 and treated biweekly for total of 6 doses (LTΒRB97) or 8 doses (LTΒRB88), respectively. While 10 mg / kg LTΒRB88 did not demonstrate significant tumor growth inhibition, 10 mg / kg LTΒRB97 treatment resulted in CT-26 tumor growth inhibition of 48.94% (on day 23; p<0.0001) in Balb / c mice and resulted in significantly increased life span of CT-26 tumor bearing Balb / c mice (by 40.91%, p = 0.018)(Table 18). Based on the positive results, in particularly of LIGHT fusion proteins, subsequent studies were performed with the murine colon carcinoma CT26 (parental; 3 × 105cells / mouse) and MC38- hMSLN (2.5 × 105cells / mouse) or CT26-hEGFR (5 × 106cells / mouse) cell lines implanted subcutaneously in Balb / c mice (CT26 and CT26-hEGFR) or C57BL / 6 mice (C57BL / 6NCrl, Charles River; MC38-hMSLN) to evaluate different tumor antigen-targeting LTβR bispecific antibodies alone and in combination with immune checkpoint blocking α-PD-1 treatment. The studies comprised groups of 10 mice (CT26 and MC38-hMSLN) or 20 mice (CT26-hEGFR), each bearing a single tumor. On day 10 (CT26-hEGFR at individual tumor volumes of 48 mm³ to 75 mm³) or day 13 (CT26 at tumor volumes of 50 mm³ to 100 mm³ and MC38-hMSLN at individual tumor volumes of 32 mm³ to 88 mm³), mice were distributed among the groups, aiming at comparable group mean and median tumor volumes. TAA-targeting bsAbs were evaluated compared to a vehicle control (PBS) as well as an anti-PD-1 antibody alone or in combination. Treatment started on the day of randomization and was performed twice per week (intraperitoneally). Tumor growth inhibition was determined at the end of the treatment period by the comparison of changes in tumor volumes of the test groups relative to changes in the PBS treated control group and was expressed as % TGI. Mice were further followed for survival and euthanized at tumor volume >1000 mm3. The experiment evaluating the activity of EDB × LTβR- bivalent bsAb (LTBRB401) was terminated on day 39. At a 10 mg / kg dose LTβRB401 achieved significant tumor growth inhibition alone (55%, p < 0.0001) and in combination with anti-PD-1 Ab (63%, p < 0.0001) in tumor bearing BALB / c mice. LTΒRB401 similarly displayed a significant increase in life span alone or in combination with anti-PD-1 Ab. Tumor growth inhibition with 10093699.0207 PATENT mg / kg LTBRB401 in combination with α-PD-1 Ab was significantly improved compared to α-PD- 1 Ab alone (p<0.0001) (Figure 18). The study evaluating the activity of EGFR × LTβR-bivalent bsAb (LTBRB398) was terminated on day 67. At a 10 mg / kg dose LTBRB398 achieved significant tumor growth inhibition alone (68%, p < 0.0001; with 6 / 20 complete responses (CR)) and in combination with anti-PD-1 Ab (106%, p < 0.0001; with 20 / 20 CR) in tumor bearing BALB / c mice (Figure 19). Anti-PD-1 Ab similarly displayed a significant tumor growth inhibition alone (103%, p < 0.0001; with 17 / 20 CR). In the study evaluating the activity of MSLN × LTβR-bivalent bsAb (LTBRB399) two doses of LTBRB399 were tested, 10 mg / kg and 20 mg / kg. At a 10 mg / kg dose LTBRB399 achieved significant tumor growth inhibition alone (50%, p < 0.05) and in combination with anti-PD-1 Ab at both doses (64%, p < 0.001 at 10 mg / kg and 69%, p < 0.0001 at 20 mg / kg) in tumor bearing C57BL / 6 mice. Tumor growth inhibition with 20 mg / kg LTBRB399 in combination with α-PD-1 Ab was significantly improved compared to α-PD-1 Ab alone (p < 0.05)(Figure 20A). Summary of the results of these combination studies is provided in Table 18. In a separate efficacy experiment evaluating the potential of RE mutations to improve the in vivo anti-tumor activity of LTβR-agonistic bsAbs, the murine colon carcinoma CT26-hMSLN cell line was implanted subcutaneously (1 × 105cells / mouse) in Balb / c mice. The experiment comprised seven groups of 10 mice each bearing a single CT26-hMSLN tumor. On day 10, at tumor volumes of 50 mm³ to 70 mm³, mice were distributed among the groups, aiming at comparable group mean and median tumor volumes. Three MSLN-redirecting bsAbs (MSLN- bivalent × LTβR-bivalent LTBRB399, MSLN-monovalent × LTβR-bivalent RE LTBRB459 and MSLN-monovalent × LTβR-monovalent RE LTBRB435) were evaluated at two dose levels, 1 mg / kg and 10 mg / kg. Antitumor efficacy of all groups was assessed using the vehicle control group as a reference. Treatment started on the day of randomization and was performed for total of 7 doses (intraperitoneally, twice per week; 7thdose being administered on day 32). Tumor growth inhibition was determined at the end of the treatment period by the comparison of changes in tumor volumes of the test groups relative to changes in the PBS treated control group and is expressed as the delta TGI value (denoted TGI in text) in percent. Mice were further followed for survival and euthanized at a tumor volume >1000 mm3. The experiment was terminated on day 45. On day 28, the bsAbs LTβRB399 and LTΒRB459 at 10 mg / kg dose resulted in a similar trend of tumor growth inhibition (45.9% and 52.2%, respectively; all p = 0.0001) and resulted in significant increases in life span (30.4%; p = 0.134 and 35.7; p = 0.077, respectively). LTΒRB435 at a 10 mg / kg dose resulted in tumor growth inhibition of 33.0% (p = 0.0008) (Figure 20B, Table 18). Overall, the study results reported here suggest bispecific LTβR-agonistic antibodies targeting different tumor antigens have a trend of tumor growth inhibition with an increase in093699.0207 PATENT lifespan at higher dose levels. The combination of these antibodies with immune checkpoint blockers (e.g., α-PD-1) may enhance anti-tumor efficacy. Example 14: Characterization of LTBRB509 (AGB201) The present example provides data characterizing the LTBRB509 molecule, also identified as AGB201. As illustrated above and in Figure 21, the AGB201 is a homodimer comprising two heavy chains and two light chains. The IgG1 Fc of the AGB201 includes silent mutations to block binding to FcRγ receptors. Each heavy chain of the anti-EDB antibody is linked with an anti- LTβR spFv. Binding Features To evaluate the potency of AGB201, an Octet Target binding assay was performed following the manufacturer’s protocols. Briefly, biotinylated LTBR was loaded onto Octet biosensors at 1 μg / ml. Next, reference standards and samples were added in multiple doses and an EDB molecule was finally incubated before measuring the potency of the sample relative to the standards. Data on the activity of potency of the AGB201 molecule are summarized in Figures 22A and 22B and Table 19. Next, the ability of AGB201 to specifically bind cells that express LTβR was examined. LTβR+A549 cells were collected using Enzyme-free dissociation buffer (Gibco, 12151-014), and transferred in low attachment 96-wells U-bottom plate (Costar, Cat. No.7007), centrifuged at 400 × g for 4 min, and washed with PBS. Cells were stained with Near-IR live / dead stain (Thermofisher, Cat. No. L34976) according to the manufacturer’s protocol. Cells were washed with PBS as described above and thereafter incubated at room temperature for 10-15 min with Human Fc block (BD564220; 0.5 mg / ml, 2.5 mg / well). Afterward, the plate was centrifuged at 400 × g for 4 min and the supernatant was discarded. AGB201 (or corresponding silent Fc huIgG1 kappa), diluted to appropriate concentrations (final concentration range 2,360 nM – 0.0133 nM; 3- fold dilution steps) in FACS staining buffer, were added to the cells, and incubated for 35-45 min at 4 °C. Cells were washed twice with the FACS staining buffer, followed by additional 35-45 min incubation with PE-labeled goat anti-human secondary Ab (Jackson Immuno, Cat. No. 109-546- 088) and final wash, before the analysis on FACS Fortessa. The data were analyzed with FlowJo v10. The affinity of AGB201 towards the recombinant mouse LTβR (mouse LTBR-Fc (muIgG2A Fc), batch LTBRW5.001) was determined using Surface Plasmon Resonance (SPR) at 25°C.093699.0207 PATENT The concentrations, association times, and dissociation times depended on the binding characteristics of each antigen-antibody pair. In general, antigen injections were performed as multi-cycle kinetics by sequential injection of a range of antigen concentrations. Regeneration was performed between cycles with an appropriate solution. Sensorgrams were processed to determine the kinetic parameters association rate constant (ka), dissociation rate constant (kd), and equilibrium dissociation constant (KD = kd / ka). As seen in Figures 23A and 23B, AGB201 bound to LTβR+A549 cells with an EC50 of about 30 nM and a Cmax value of about 9948. Additional data obtained using SPR using AGB201 captured onto C1 chip with covalently coupled protein A / G. huLTBR-His and huFn-7-EDB-8-9 (EDB+) were tested as analytes, respectively. Running buffer used was HBS-P+BSA and the assay parameters for SCK (Single Cycle kinetics): 180 sec association, 1800 sec dissociation (50 µl / min). The SPR data are reported in Tables 20-22. Overall, LTBR509-LTBRW3 (EDB) had significant biphasic behavior therefor affinity and activity could not be reliably reported. Qualitative assessments for LTBR509 showed that none of the degradation conditions significantly impacted the activity. Epitope mapping Next, experiments for epitope mapping were performed. The epitopes of LTBRW3 (huFn- 7-EDB-8-9 (EDB+)-Sortag-His) against LTBRB509 (ΔΔG upon binding < –1 kcal / mol) were residues 1300-1314 (ITVVAAGEGIPIFED [SEQ ID NO: 2487]), 1321-1322 (GY), and 1334- 1335 (YD). HDX-MS behaviors of LTBRW3 were monitored in the presence and in the absence of LTBRB509 for 8 time points (15, 50, 150, 500, 1,500, 5,000, 15,000, and 50,000 s) at pH 7.4 at 23 ℃. The sequence numbering of LTBRW3 was converted to that of the native sequence (Uniprot ID: P02751). The sequence coverage of LTBRW3 was 100% (= 371 / 371), when digested by pepsin – FPXIII mixed bed column after quenched with 8 M urea, 1 M TCEP hydrochloride, pH 3.0. HDX-MS analysis was performed using an automated HDx3 system (LEAP Technologies, Morrisville, NC) system analogous to the previously described except the protease column was placed outside of the cold box. The columns and pump configurations were as follows: protease, pepsin / protease type XIII (protease from Aspergillus saitoi, type XIII) column (w / w, 1:1; 2.1 x 30 mm) (NovaBioAssays Inc., Woburn, MA); trap column, Acquity UPLC BEH C18 VanGuard Pre- column (Waters, Milford, MA); analytical column, Accucore Vanquish C18 (2.1 x 100 mm, 1.5 µm) (Thermo Fisher Scientific); and LC pump, Vanquish (Thermo Fisher Scientific). The loading pump (from the protease column to the trap column) was set at 600 μL / min with 0.1% aqueous093699.0207 PATENT formic acid. The gradient pump (from the trap column to the analytical column) was set from 9% to 33% acetonitrile in 0.1% aqueous formic acid in 20 min at 100 μL / min. Mass spectrometric analyses were carried out using an LTQ™ Orbitrap Fusion Lumos mass spectrometer (Thermo Fisher Scientific) with a capillary temperature at 275 °C, resolution of 120,000, and mass range (m / z) of 300 – 1,500. HDX-MS NPP3W6 epitope mapping samples were prepared by mixing LTBRW3 with DPBS with and without AGB201. H2O or a deuterated buffer (DPBS in 90% D2O) was admixed and incubated for 3 h at 55 ºC.8 M urea, 1 M TCEP, pH 4.0 was added to the above mixture and quenched solution injected into HDX-MS system (digestion and separation). Figures 24A and 24B show a paratope map of LTBRW3 against LTBRB509. The free energy change upon binding to an mAb is shown in gradient color from red to blue as shown in the right. The residues which are shown from blue to green are the HDX-MS identified epitopes. The residues which were not stabilized upon binding to the antibodies were shown yellow. The residues that exchange too fast or too slow to see the perturbation upon the binding were shown gray. The residues without color indicate the HDX behaviors were not monitored, because there is no peptide to cover the residues, or the residues are the first two residues of a peptide. Antibody Sequence Analysis The sequences of the AGB201 molecule were identified and described in Table 23. Both variable regions used in AGB201 have favorable sequence quality for PTM risk and in silico immunogenicity and / or are clinically validated (L19). Retrogenix Analysis Slides were spotted with expression vectors encoding both ZsGreen1 and human FN1 (EDB) (tethered secreted form), LTBR, and used to reverse-transfect HEK293 cells. AGB201 or Rituximab biosimilar or PBS only was added to the above cells / slides after fixation. Slides were subsequently incubated with an AlexaFluor647 labeled anti-human IgG Fc detection antibody, followed by fluorescence imaging. This detection antibody has been validated previously for use in the Retrogenix Cell Microarray system for detecting human IgGs. Flow cytometry dose response validation study in HEK293 cells: HEK293 cells were transfected with expression vectors encoding ZsGreen1 only, or ZsGreen1 and LTBR or FN1 (EDB) (tethered secreted form). Live cell transfectants were incubated with a dose range (0.018 – 300 ^g / mL) of AGB201 or assay buffer only, as indicated. Cells were washed and incubated with the same AF647 anti-hIgG Fc detection antibody. Cells were again washed and analyzed by flow cytometry. A 7AAD live / dead dye was used to exclude dead cells, and ZsGreen+(transfected) cells were selected for analysis.093699.0207 PATENT AGB201 was screened for binding against fixed HEK293 cells, individually expressing 6105 full-length human plasma membrane proteins, secreted and cell surface-tethered human- secreted proteins plus a further 400 human heterodimers. The screen revealed 36 library interactions. After removing 12 interactions that were due to other test articles from the pool, 15 interactions were observed with the test article and negative controls, and therefore designated as non-specific, and 3 interactions were classed as non-significant, 6 specific interactions for test article AGB201 were identified on fixed cells. These were the primary targets, LTBR and FN1 (EDB) as well as PCDH7 and COL6A2 (UCNs 5610, 5647 and 5648, isoforms 2C2, 2C2A’ and 2C2A respectively). When these interactions were investigated further, in a single dose flow cytometry study, AGB201 was screened against COL6A2 (UCN 6510, isoform 2C2, secreted form) and showed no significant binding to COL6A2 on either live or fixed cells. In a dose-response flow cytometry study, AGB201 showed dose-related binding to LTBR, a primary target, with an EC50 value of 0.09 μg / mL. Dose-related binding was also observed with PCDH7 with an EC50 of 39.6 μg / mL. AGB201 showed significant binding to FN1 (EDB) but an EC50 could not be determined for the interaction due to the dose-related background binding of AGB201 to ZsGreen1 transfected HEK293 cells. Figures 25A-25C and Table 24 show data related to AGB201 binding to HEK293 transfected cells. In order to alleviate the high background binding observed in HEK293 cells, the binding of AGB201 was investigated in CHOK1 cells. For flow cytometry single dose flow cytometry validation study in CHOK1 cells, CHOK1 cells were transfected with expression vectors encoding ZsGreen1 only, or ZsGreen1 and FN1 (EDB) (tethered secreted form). Live cell transfectants were incubated with 50 µg / mL AGB201 or assay buffer only, as indicated. Cells were washed and incubated with the same AF647 anti-hIgG Fc detection antibody. Cells were again washed and analysed by flow cytometry. A 7AAD live / dead dye was used to exclude dead cells, and ZsGreen+(transfected) cells were selected for analysis. For flow cytometry dose response validation study in CHOK1 cells, CHOK1 cells were transfected with expression vectors encoding ZsGreen1 only, or ZsGreen1 and LTBR, FN1 (EDB) (tethered secreted form). Live cell transfectants were incubated with a dose range (0.018 – 300 ^g / mL) of AGB201 or assay buffer only, as indicated. Cells were washed and incubated with the same AF647 anti-hIgG Fc detection antibody as used in the cell microarray screens. Cells were again washed and analysed by flow cytometry. A 7AAD live / dead dye was used to exclude dead cells, and ZsGreen+(transfected) cells were selected for analysis.093699.0207 PATENT AGB201 showed significant binding to FN1 (EDB). Control antibody LTBR x null showed no binding to FN1 (EDB). In a dose-response study performed on CHOK1 cells, AGB201 showed dose-related binding to LTBR and FN1 (EDB), the primary targets, with EC50values of 0.092 and 0.2 ^g / mL respectively. The test article also showed dose-related binding to PCDH7 with an EC50 of 102 μg / mL. Control antibody null x EDB showed dose-related binding to FN1 (EDB) and PCDH7, with EC50 values of 0.066 and 149 µg / mL respectively, and no significant binding to LTBR. Control antibody LTBR x null showed dose-related binding to LTBR with an EC50of 0.034 µg / mL, and no significant binding to either FN1 (EDB) or PCDH7. These data indicate that LTBRB509.003 binds its primary targets, LTBR and FN1 (EDB) and has a secondary interaction with PCDH7, mediated through the FN1 (EDB) binding arm. Figures 25D and 25E and Tables 25 and 26 show data related to AGB201 binding to CHOK1 transfected cells. Animal studies (murine) Next, the efficacy of the AGB201 molecule was tested in mice. Female CD1 mice (ages 6-8 weeks of age) were obtained from Taconic Labs and were grouped and housed in filtered top plastic cages. Mice were maintained on Laboratory Rodent Chow (PMI). On Day 0 of the study, all mice received an intravenous injection of 10 mg / kg, 1 mg / kg, or 30 mg / kg of AGB201. For diluted whole blood plasma micro-sampling, mice were bled at the designated time points via tail snip into micro EDTA tubes to obtain 15-20µL of whole blood plasma. Whole blood plasma collected was diluted 1:10 in LowCross-Buffer (e.g., 15µL whole blood plasma + 135µL buffer), inverted to mix, and kept on wet ice. Immediately after all samples were collected at a specific time point, diluted samples were centrifuged at 1500 rcf for 2 minutes at 4°C. The supernatant was pipetted into new labeled tubes and frozen at -800C until completion of the last timepoint at which time all samples were stored for the analysis. Overall, intravenous biweekly injections provided adequate coverage above target-mediated drug disposition (TMDD). In particular, as shown in Figures 26A and 26B, (i) single dose IV study with AGB201 had nonlinear PK at 1 mg / kg, 10 mg / kg, and 30 mg / kg; (ii) TMDD observed at all doses was due to LTβR binding; (iii) multiple doses at 30 mg / kg showed sustained exposure maintained for 2 weeks; and (iv) TMDD impact expected to be saturated at doses ^ 30 mg / kg. Next, multiple doses were tested in CD1 mice. As seen in Figures 26C and 26D, significant differences in PK between null x EDB and AGB201 (LTBRxEDB) indicate TMDD at all doses tested, while no main difference was observed in the capture methods (e.g., EDB vs. LTBR). PK studies (simian) Next, studies were performed to determine the pharmacokinetics, pharmacodynamics, and potential toxicity of LTBRB509, when given intravenously as a single dose to Cambodian093699.0207 PATENT cynomolgus monkeys. AGB201 was administered by intravenous slow bolus injection on Day 1. The animals were temporarily restrained for dose administration and were not anesthetized. The animals were observed within their cages (unless necessary for identification or confirmation of possible findings) at least once daily. Clinical pathology samples were collected pretreatment, on Day 1 (6 hours post-dose), Day 2 (24 hours post-dose), Day 5 (96 hours post-dose), and Day 8 (168 hours post-dose). Standard hematology, coagulation, and clinical chemistry parameters were determined, and a blood smear was prepared from each hematology sample. Urine was collected pretreatment and on Day 8 (168 hours post-dose). Samples for immunophenotyping were collected at the following time points post-dosing: 6 hours, 24 hours, 96 hours, 168 hours, concurrently with hematology samples as scheduling permitted. The following two flow cytometry antibody panels were used: CD4, CD127, CD45, CD16, CD25, CD3, CD69 and CD8; and HLA-DR, CD159a, CD45, CD16, CD14, CD80, CD20 and CD86. For activation markers, fluorescence minus one gating strategy was applied to analyze the induction of activation. Bioanalytical samples were collected at the following time points post-dose: 1 hour, 6 hours, 24 hours, 48 hours, 96 hours, 168 hours, 240 hours, 336 hours, 456 hours, 576 hours, 696 hours. Samples were allowed to clot at ambient temperature before centrifugation. The samples were centrifuged, and the resultant serum was separated, split into 2 approximately equal aliquots in uniquely labeled polypropylene tubes, and frozen immediately over dry ice or in a freezer set to maintain -80°C. The samples were stored at -70°C or colder until analysis. Serum samples were analyzed for concentration of AGB201 using a fit-for-purpose analytical procedure. The biotinylated huFn-7-EDB-8-9 (EDB+) human fibronectin was coated onto an MSD streptavidin 96-well plate. AGB201 in standards (STDs), quality control (QC), or study samples bound to the immobilized capture reagent. The plate-bound AGB201 was detected by Sulfo-Tag-labeled Ru- R10Z8E9 (detection antibody) to generate the ECL signals. The intensity of the ECL signal was proportional to the amount of AGB201 in calibration STDs, QC samples, and test samples. Cytokine sample collection was performed a week before dosing, and at the following time points post-dosing: Day 1 (2 hours), Day 1 (6 hours), Day 2 (24 hours), Day 4 (72 hours). The samples were centrifuged, and the resultant plasma was separated, transferred split into 3 approximately equal aliquots in uniquely labeled polypropylene tubes, and frozen immediately over dry ice or in a freezer set to maintain -80°C. The following cytokines analyses were conducted for each time point, using the appropriate assays for plasma: IL-1β, IL-1ra, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12 / 23 (p40), IL-13, IL-17A, MCP-1, MIP-1β, IFN-γ, TNF-α, G-CSF, and GM-CSF, and093699.0207 PATENT IP-10. The sample collections for determination of soluble LTBR and chemokines I-TAC, MIP3α, CCL19, and CXCL12, respectively, were performed similarly, with the only difference being that instead of the time point Day 1 (2 hours post-dosing), Day 7 (168 hours post-dosing) collection was performed. Following a single IV dose, serum AGB201 exposure (maximum concentration observed [Cmax] and area un...

Claims

093699.0207 PATENT WHAT IS CLAIMED IS:

1. A multispecific binding molecule comprising a binding domain that specifically binds to LTβR or a fragment or derivative thereof and a binding domain that specifically binds to EDB or a fragment or derivative thereof, wherein the binding domain that specifically binds to LTβR comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising: (a) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701; (b) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 762, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 763; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 730; (c) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 770; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 773; (d) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 798; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 801; or (e) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 727; and the VL comprises093699.0207 PATENT an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO:

767.

2. The multispecific binding molecule of claim 1, wherein the VH of comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO:

701.

3. The multispecific binding molecule of claim 1 or 2, wherein the VH comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO:

511.

4. The multispecific binding molecule of any one of claims 1-3, wherein the VL comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO:

513.

5. The multispecific binding molecule of any one of claims 1-4, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO:

511.

6. The multispecific binding molecule of any one of claims 1-5, wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO: 513.093699.0207 PATENT 7. The multispecific binding molecule of any one of claims 1-6, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 44, SEQ ID NO: 250, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 288, SEQ ID NO: 473, SEQ ID NO: 499, SEQ ID NO: 501, or SEQ ID NO: 511; and the VL comprises the amino acid sequence set forth in SEQ ID NO: 5, SEQ ID NO: 29, SEQ ID NO: 33, SEQ ID NO: 46, SEQ ID NO: 251, SEQ ID NO: 273, SEQ ID NO: 277, SEQ ID NO: 290, SEQ ID NO: 474, SEQ ID NO: 496, SEQ ID NO: 500, or SEQ ID NO:

513.

8. The multispecific binding molecule of any one of claims 1-7, wherein (a) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 251; (b) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 474; (c) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 5; (d) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 29; (e) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 496; (f) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 273; (g) the VH comprises the amino acid sequence set forth in SEQ ID NO: 34 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (h) the VH comprises the amino acid sequence set forth in SEQ ID NO: 278 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; (i) the VH comprises the amino acid sequence set forth in SEQ ID NO: 501 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500; (j) the VH comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 46; (k) the VH comprises the amino acid sequence set forth in SEQ ID NO: 288 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 290; (l) the VH comprises the amino acid sequence set forth in SEQ ID NO: 511 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 513;093699.0207 PATENT (m) the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (n) the VH comprises the amino acid sequence set forth in SEQ ID NO: 276 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; or (o) the VH comprises the amino acid sequence set forth in SEQ ID NO: 499 and the VL comprises the amino acid sequence set forth in SEQ ID NO:

500.

9. The multispecific binding molecule of any one of claims 1-8, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO:

251.

10. The multispecific binding molecule of any one of claims 1-9, wherein the binding domain that specifically binds to LTβR comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226.

11. The multispecific binding molecule of any one of claims 1-10, wherein the binding domain that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226.

12. The multispecific binding molecule of any one of claims 1-11, wherein the binding domain that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2197.

13. The multispecific binding molecule of any one of claims 1-12, wherein the binding domain that specifically binds to EDB or a fragment or derivative thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 704; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 707.093699.0207 PATENT 14. The multispecific binding molecule of claim 13, wherein the binding domain that specifically binds to EDB comprises a heavy chain variable region (VH) comprising an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO:

6.

15. The multispecific binding molecule of claim 13 or 14, wherein the binding domain that specifically binds to EDB comprises a light chain variable region (VL) comprising an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO:

7.

16. The multispecific binding molecule of any one of claims 13-15, wherein the binding domain that specifically binds to EDB comprises a VH comprising the amino acid sequence set forth in SEQ ID NO:

6.

17. The multispecific binding molecule of any one of claims 13-16, wherein the binding domain that specifically binds to EDB comprises a VL comprising the amino acid sequence set forth in SEQ ID NO:

7.

18. The multispecific binding molecule of any one of claims 13-17, wherein the binding domain that specifically binds to EDB comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 6 and a VL comprising the amino acid sequence set forth in SEQ ID NO:

7.

19. The multispecific binding molecule of claims any one of claims 1-18, which is a bispecific antibody.

20. A multispecific binding molecule comprising a first heavy chain (HC1), a first light chain (LC1), a second heavy chain (HC2), and a second light chain (LC2), wherein the HC1 is fused to a first antigen-binding fragment that specifically binds to LTβR and the HC2 is fused to a second antigen-binding fragment that specifically binds to LTβR, and wherein (a) each of the HC1 and HC2 comprises a heavy chain variable region (VH) comprising an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 702, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 703, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 704;093699.0207 PATENT (b) each of LC1 and LC2 comprises a light chain variable region (VL) comprising an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 705, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 706, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 707; and (c) each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising: (i) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 701; (ii) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 761, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 762, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 763; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 764, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 730; (iii) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 768, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 769, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 770; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 771, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 772, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 773; (iv) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 796, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 797, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 798; and the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 799, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 800, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 801; or (v) the VH comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 765, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 766, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 727; and093699.0207 PATENT the VL comprises an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 728, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 729, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO:

767.

21. The multispecific binding molecule of claim 20, wherein each of the first antigen- binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR comprises an HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 696, an HCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 697, and an HCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 698, an LCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 699, an LCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 700, and an LCDR3 comprising the amino acid sequence set forth in SEQ ID NO:

701.

22. The multispecific binding molecule of claim 20 or 21, wherein each of the HC1 and HC2 comprises a VH comprising the amino acid sequence set forth in SEQ ID NO:

6.

23. The multispecific binding molecule of any one of claims 20-22, wherein each of the LC1 and LC2 comprises a VL comprising the amino acid sequence set forth in SEQ ID NO:

7.

24. The multispecific binding molecule of any one of claims 20-23, wherein each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR comprises: (a) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 251; (b) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 474; (c) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 5; (d) the VH comprises the amino acid sequence set forth in SEQ ID NO: 4 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 29; (e) the VH comprises the amino acid sequence set forth in SEQ ID NO: 473 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 496; (f) the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 273;093699.0207 PATENT (g) the VH comprises the amino acid sequence set forth in SEQ ID NO: 34 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (h) the VH comprises the amino acid sequence set forth in SEQ ID NO: 278 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; (i) the VH comprises the amino acid sequence set forth in SEQ ID NO: 501 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 500; (j) the VH comprises the amino acid sequence set forth in SEQ ID NO: 44 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 46; (k) the VH comprises the amino acid sequence set forth in SEQ ID NO: 288 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 290; (l) the VH comprises the amino acid sequence set forth in SEQ ID NO: 511 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 513; (m) the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 33; (n) the VH comprises the amino acid sequence set forth in SEQ ID NO: 276 and the VL comprises the amino acid sequence set forth in SEQ ID NO: 277; or (o) the VH comprises the amino acid sequence set forth in SEQ ID NO: 499 and the VL comprises the amino acid sequence set forth in SEQ ID NO:

500.

25. The multispecific binding molecule of any one of claims 20-24, wherein each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR comprises the VH comprises the amino acid sequence set forth in SEQ ID NO: 250 and the VL comprises the amino acid sequence set forth in SEQ ID NO:

251.

26. The multispecific binding molecule of any one of claims 20-25, wherein each of the first antigen-binding fragment that specifically binds to LTβR and the second antigen-binding fragment that specifically binds to LTβR is a stapled single chain Fv (spFv).

27. The multispecific binding molecule of claim 26, wherein the spFv comprises the amino acid sequence set forth in SEQ ID NO: 2197, SEQ ID NO: 2198, SEQ ID NO: 2221, SEQ ID NO: 2222, SEQ ID NO: 2227, SEQ ID NO: 2228, SEQ ID NO: 2241, SEQ ID NO: 2242, SEQ ID NO: 2225, or SEQ ID NO: 2226.093699.0207 PATENT 28. The multispecific binding molecule of claim 26 or 27, wherein the spFv comprises the amino acid sequence set forth in SEQ ID NO: SEQ ID NO: 2197.

29. The multispecific binding molecule of any one of claims 20-28, wherein each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2174.

30. The multispecific binding molecule of any one of claims 20-28, wherein each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2174.

31. The multispecific binding molecule of any one of claims 20-28, wherein each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2105 or 2486.

32. The multispecific binding molecule of any one of claims 20-28, wherein each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2105 or 2486.

33. The multispecific binding molecule of any one of claims 20-32, wherein each of the LC1 and LC2 comprises an amino acid sequence that is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 2087.

34. The multispecific binding molecule of any one of claims 20-32, wherein each of the LC1 and LC2 comprises the amino acid sequence set forth in SEQ ID NO: 2087.

35. The multispecific binding molecule of any one of claims 20-34, wherein093699.0207 PATENT (a) each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2174; and (b) each of the LC1 and LC2 comprises the amino acid sequence set forth in SEQ ID NO: 2087.

36. The multispecific binding molecule of any one of claims 20-34, wherein (a) each of the HC1 fused to the first antigen-binding fragment that specifically binds to LTβR and the HC2 fused to the second antigen-binding fragment that specifically binds to LTβR comprises the amino acid sequence set forth in SEQ ID NO: 2105 or 2486; and (b) each of the LC1 and LC2 comprises the amino acid sequence set forth in SEQ ID NO: 2087.

37. The multispecific binding molecule of claims any one of claims 1-18, which is a bispecific antibody.

38. A multispecific binding molecule comprising (a) a first polypeptide that specifically binds to LTβR and EDB; (b) a second polypeptide that specifically binds to EDB; (c) a third polypeptide that specifically binds to LTβR and EDB; (d) a fourth polypeptide that specifically binds to EDB; wherein each of the first polypeptide and the third polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2174, and wherein each of the second polypeptide and the fourth polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2087.

39. A multispecific binding molecule comprising (a) a first polypeptide that specifically binds to LTβR and EDB; (b) a second polypeptide that specifically binds to EDB; (c) a third polypeptide that specifically binds to LTβR and EDB; (d) a fourth polypeptide that specifically binds to EDB; wherein each of the first polypeptide and the third polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2105 or 2486, and093699.0207 PATENT wherein each of the second polypeptide and the fourth polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 2087.

40. The multispecific binding molecule of claim 38 or 39, which is a bispecific antibody.

41. A nucleic acid molecule encoding the multispecific binding molecule of any one of claims 1-40.

42. A vector comprising the nucleic acid molecule of claim 41.

43. A host cell comprising the nucleic acid molecule of claim 41 or the vector of claim 42.

44. A composition comprising the multispecific binding molecule of any one of claims 1- 40.

45. The composition of claim 44, which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

46. A method of producing a multispecific binding molecule, the method comprising: (a) culturing the host cell of claim 43; and (b) harvesting the molecule.

47. A method of treating a cancer in a subject in need thereof, comprising administering to the subject an effective amount of the multispecific binding molecule of any one of claims 1-40, the nucleic acid molecule of claim 41, the vector of claim 42, or the composition of claim 44 or 45.

48. The method of claim 47, further comprising administering a second therapeutic agent selected from the group consisting of an anti-CD20 mAb, an anti-TIM-3 mAb, an anti-CTLA-4 antibody, an anti-PD-L1 antibody, an anti-PD-1 antibody, a PD-1 / PD-L1 therapy, Indoleamine- pyrrole 2,3-dioxygenase (IDO), an anti-OX40 antibody, an anti-GITR antibody, an anti-CD40 antibody, an anti-CD38 antibody, a cytokine, an oncolytic virus, a TLR agonist, a STING agonist, and combinations thereof.

49. The method of claim 47 or 48, wherein the cancer is a lung cancer, a bladder cancer, a head and neck cancer, an esophageal cancer, a vaginal cancer, a pancreatic cancer, a colon cancer, a093699.0207 PATENT liver cancer, uterine cancer, an ovarian cancer, a breast cancer, a prostate cancer, a stomach cancer, a melanoma, a glioblastoma (GBM), an endometrial cancer, a soft tissue carcinoma, or a mesothelioma.

50. The method of claim 49, wherein the lung cancer is a small cell lung cancer, a non small cell lung cancer (NSCLC), an adenocarcinoma, a squamous lung cancer and / or carcinoma, or a large cell carcinoma.

51. The method of claim 49, wherein the bladder cancer is a urinary bladder cancer, a metastatic bladder cancer, a muscle invasive bladder cancer, or a non-invasive bladder cancer.

52. The method of claim 49, wherein the head and neck cancer is a pharynx cancer, a larynx cancer, or an oral cavity cancer.

53. The method of claim 49, wherein the cancer is an esophageal cancer.

54. The method of claim 49, wherein the vaginal cancer is a cancer of the vulva, a cancer of the vagina, or a cancer of the cervix.

55. The method of claim 49, wherein the cancer is a pancreatic cancer.

56. The method of claim 49, wherein the cancer is a colon cancer, a colorectal cancer, a cancer of the small intestines, a gastrointestinal cancer, or a rectal cancer.

57. The method of any one of claims 47-56, wherein the cancer is an EDB-expressing cancer or a cancer with a high prevalence of EDB expression.

58. A method of activating non-canonical NF-κB signaling in a subject in need thereof, comprising administering to the subject an effective amount of the multispecific binding molecule of any one of claims 1-40, the nucleic acid molecule of claim 41, the vector of claim 42, or the composition of claim 44 or 45.

59. A method of inducing tertiary lymphoid structure (TLS) neogenesis in a subject in need thereof, comprising administering to the subject an effective amount of the multispecific binding093699.0207 PATENT molecule of any one of claims 1-40, the nucleic acid molecule of claim 41, the vector of claim 42, or the composition of claim 44 or 45.

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