SIRP-GAMMA INHIBITION FOR CANCER TREATMENT

Abstract

The present invention relates to a composition for use in the treatment of a subject with a tumor or cancer, wherein the composition comprises a SIRP antigen-binding protein that binds to domain 1 (D1) and domain 2 (D2) of immunoglobulin (Ig) SIRP.

Description

SIRP-GAMMA INHIBITION FOR CANCER TREATMENT CROSS-REFERENCE WITH RELATED APPLICATIONS This application claims priority with respect to U.S. Provisional Patent Application No. 62 / 865,537, filed on June 24, 2019, the full content of which is incorporated herein by reference in its entirety. INCORPORATION BY REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY A complete computer-readable nucleotide / amino acid sequence list is incorporated by reference, which is presented with this document and is identified as follows: an 89,857-byte ASCII (text) file named A-2396_Seqlisting.txt; created on June 9, 2020. BACKGROUND Blocking immune checkpoints has been shown to induce long-lasting immune responses against various cancers. However, patient responses to immunotherapies, such as anti-PD1 / PD-L1, are limited to only a small percentage of patients. PD-1 is one of many co-inhibitory receptors expressed on T lymphocytes that are upregulated during T lymphocyte activation, and its interaction with PD-L1 limits T lymphocyte activation. Although anti-PD-1 sufficiently blocks the inhibitory pathway and rejuvenates T lymphocytes within various tumors, many other inhibitory receptors may be expressed on T lymphocytes. Therefore, the exploration and subsequent identification of novel inhibitory receptors on T lymphocytes will broaden the targets of immunotherapy and greatly improve its efficacy in treating cancer. SUMMARY This paper presents, for the first time, data demonstrating that SIRPy is a potential novel inhibitory receptor on human T lymphocytes. These data were surprising given previous studies that suggested SIRPy as a T-cell costimulatory molecule (Piccio et al., Blood 105(6):2421–2427 (2005); Leitner et al., Immunol Letters 128(2):89–97 (2010)). The expression, regulation, and function of SIRPy were evaluated, and it was shown that SIRPy is primarily expressed on activated T and NK cells, and is highly expressed on CD8 memory T cells and tumor-infiltrating exhausted T cells.Furthermore, this paper demonstrates that SIRPy overexpression inhibited the release of effector cytokines from CD8 T lymphocytes, while inactivated SIRPy expression (via CRISPR) enhanced T lymphocyte effector states, as measured by T lymphocyte proliferation and T lymphocyte-mediated cytokine production. Additionally, SIRPy overexpression in human Treg lymphocytes leads to enhanced Treg suppressor function. Additionally, the data in this document support that blocking the interaction between CD47 and SIRPy is not a requirement for achieving increased T lymphocyte proliferation and IFNy secretion, that the T lymphocyte inhibitory function of SIRPy may be mediated through a SIRPy-specific epitope, and that molecules that bind to the D1 and D2 interface of SIRPy may be useful for enhancing T lymphocyte function. Without being tied to any particular theory, these data support the use of SIRPy-binding molecules, for example, SIRPy inhibitors, to increase effector activity or reduce T-cell suppressor activity in a subject, ultimately for the treatment of a tumor or cancer in that subject. Accordingly, in one embodiment, the present invention relates to a method for treating a tumor or cancer in a subject, comprising administering to the subject an effective amount of a SIRPy-binding molecule, for example, a SIRPy inhibitor. The present disclosure also provides methods for increasing effector activity or reducing T-cell suppressor activity in a subject with a tumor or cancer.In exemplary embodiments, the method comprises administering to the subject a SIRPy-binding molecule, for example, a SIRPy inhibitor, in an amount effective to increase effector activity or decrease suppressor activity in the subject. Methods for enhancing an immune response against a tumor or cancer in a subject are further provided herein. In exemplary embodiments, the method comprises administering to the subject a SIRPy-binding molecule, for example, a SIRPy inhibitor, in an amount effective to enhance an immune response against a tumor or cancer. In various aspects, the subject has hepatocellular carcinoma (HCC), colorectal cancer (CRC), lung cancer, or breast cancer, optionally, where the subject has non-small cell lung cancer (NSCLC). In some cases, the SIRPy-binding molecule binds to the immunoglobulin (Ig) domain 1 (D1). In some cases, the SIRPy-binding molecule binds to both the D1 and D2 domains of SIRPy. In some cases, the SIRPy-binding molecule binds to both D1 and D2, optionally at the interface between D1 and D2. In some cases, the SIRPy-binding molecule binds to the epitope to which the SIRPy monoclonal antibody 0X117 binds, optionally competing with a reference antibody known to bind to SIRPy (e.g., 0X117) for SIRPy binding. The SIRPy-binding molecule in various cases binds to SIRPy with the same or greater affinity than OX117, optionally where the SIRPy-binding molecule is OX117, or an antigen-binding fragment thereof. The SIRPy-binding molecule in various aspects forms hydrogen bonds with one or more of the amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPy.The SIRPy-binding molecule, in some respects, induces a conformational change in SIRPy upon binding to it. In several cases, the SIRPy-binding molecule binds simultaneously to two SIRPy molecules or promotes dimerization of SIRPy. SIRPy. Optionally, the SIRPy-binding molecule binds to an epitope that does not overlap with the CD47-binding site. In many respects, the SIRPy-binding molecule is an antigen-binding protein that binds to SIRPy. Optionally, the antigen-binding protein is an antibody, an antigen-binding antibody fragment, or an antibody protein product. In some respects, the antigen-binding protein binds to an epitope within the CD47-binding site of SIRPy. In several of the currently reported methods, the SIRPy-binding molecule is a SIRPy inhibitor. In some cases, the SIRPy inhibitor reduces SIRPy expression in the subject's cells, optionally reducing SIRPy expression on the cell surface of the subject's T lymphocytes. Optionally, the T lymphocytes are effector T lymphocytes of the subject. In several cases, the SIRPy inhibitor reduces a binding interaction between SIRPy and a SIRPy-binding partner, optionally CD47. In examples of currently published methods for increasing effector activity or reducing suppressor activity of T lymphocytes in a subject with a tumor or cancer, the T lymphocytes are located within a tumor or tumor microenvironment. In some cases, the T lymphocytes are tumor-infiltrating T lymphocytes. In some cases, the T lymphocytes are regulatory T lymphocytes (Tregs). In some examples, the T lymphocytes are depleted T lymphocytes, optionally, depleted CD8+ T lymphocytes. In some examples, the T lymphocytes are memory lymphocytes, optionally, CD8+ memory lymphocytes or central CD4+ memory lymphocytes. In some examples of currently published methods for enhancing an immune response against a tumor or cancer in a subject, the immune response is mediated by T lymphocytes. In various cases, T lymphocytes are located within a tumor or tumor microenvironment. In some cases, the T lymphocytes are tumor-infiltrating T lymphocytes. In some cases, the T lymphocytes are regulatory T lymphocytes (Tregs). In some examples, the T lymphocytes are exhausted T lymphocytes, or optionally, exhausted CD8+ T lymphocytes. In some examples, the T lymphocytes are memory lymphocytes, or optionally, CD8+ memory lymphocytes or central CD4+ memory lymphocytes. This disclosure further provides methods for treating a subject with a tumor or cancer. In example embodiments, the method comprises enhancing an immune response against the tumor or cancer in the subject in accordance with any one of the currently disclosed methods for enhancing an immune response against a tumor or cancer in a subject. In example embodiments, the method comprises increasing the effector activity or reducing the suppressive activity of T lymphocytes in the subject in accordance with any one of the currently disclosed methods for increasing the effector activity or reducing the suppressive activity of T lymphocytes in a subject with a tumor or cancer. The following provides additional realizations and aspects of currently disclosed pharmaceutical compositions and methods. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A–1C demonstrate that SIRPy is expressed in human T lymphocytes and NKT cells. Figure 1A is a series of FACS plots showing that the antibody against SIRPy specifically detected overexpressed SIRPy in 293T cells. Figure 1B is a series of FACS plots showing SIRPy expression in different cell types derived from human peripheral blood mononuclear cells (PBMCs). Figure 1C shows that the level of SIRPy expression in T lymphocytes does not change upon TCR stimulation. Figures 2A and 2B demonstrate that SIRPy is highly expressed in memory T cells. Figure 2A is a series of FACS plots showing expression in different T cell subsets. CD8+ memory T cells have higher SIRPy expression than CD8+ effector T cells in human SCM samples. Figure 2B is a quantification of the mean fluorescence intensity (MFI) of SIRPy expression in different T cell subsets from four different healthy SCM donors. Significance is indicated as ***p < 0.0002, **p < 0.0021, *p < 0.0332, and ns p > 0.05 using a paired t-test. Error bars represent ± ETM. Figures 3A–3C demonstrate that SIRPy has increased expression in tumor-infiltrating exhaustion T lymphocytes. Figure 3A is a graph comparing SIRPy expression in different subsets of tumor-infiltrating T lymphocytes from HCC samples. Figure 3B is a graph comparing SIRPy expression in different subsets of tumor-infiltrating T lymphocytes from CRC samples. Figure 3C is a graph comparing SIRPy expression in different subsets of tumor-infiltrating T lymphocytes from lung cancer samples. SIRPy exhibited a highly specific expression pattern in both tumor Treg (CD4-CTLA4) and exhausted CD8 T (CD8-LAYN) lymphocytes, marked with a star. Figure 4 demonstrates that SIRPy expression has increased in exhausted T lymphocytes due to repeated TCR restimulation. Figure 4 is a series of FACS graphs showing SIRPy expression in in vitro restimulated exhausted T lymphocytes and conventional T lymphocytes from three different healthy donors. Figures 5A–5D demonstrate that SIRPy overexpression in T lymphocytes inhibited IFNγ secretion. Figure 5A is a schematic diagram showing the experimental flow of SIRPy overexpression and T lymphocyte restimulation. PanT cells were isolated from human ινΐΛ / a / zuz ι / ui and activated using aCD3 / CD28 Dynabeads for 3 days. Activated T lymphocytes were infected with retroviruses (RVs) to overexpress SIRPy (RV-SIRPy) or infected with an RV vector lacking the SIRPy coding sequence as a control (RV-Vec). Five days post-infection by centrifugation, CD4 or CD8 GFP+ T lymphocytes were sorted by FACS and allowed to stand for 2 days with human IL-2. Resting T lymphocytes were then restimulated with soluble aCD3 and CD28 antibodies bound to a plate for 24 hours. The cell supernatant was collected for ELISA analysis.Figure 5B is a series of flow cytometry graphs showing human SIRPy expression in both CD4+ and CD8+ T lymphocytes. Three days post-infection by centrifugation, the cells were stained with antibody to human SIRPy. Figure 5C shows a human IFNy ELISA in the cell supernatant. Significance is indicated as ****p < 0.0001, ***p < 0.0002, **p < 0.0021, *p < 0.0332, and ns p > 0.05 using the two-way ANOVA test in GraphPad Prism. Error bars represent ± ETM. Data represent at least five independent experiments. Figure 5D shows a paired t-test of the human IFNy ELISA in the cell supernatant from five independent experiments. * indicates a p-value of <0.05 using a paired t-test. Figures 6A–6F demonstrate that knockdown of SIRPy expression in T lymphocytes enhanced IFNγ secretion. Figure 6A is a schematic diagram showing the experimental flow of SIRPy knockdown and T lymphocyte restimulation. PanT cells were isolated from human sympathetic cellular progenitor cells (SSCCs) and activated using aCD3 / CD28 Dynabeads for 2 days. Activated T lymphocytes were transfected with CRISPR guide RNA (gRNA) targeting the SIRPy genomic region to knockdown SIRPy expression in T lymphocytes or transfected with a control. Three days post-transfection, the T lymphocytes were activated with aCD3 / CD28 for 24 hours before FACS sorting. SIRPy- CD4 or CD8 T lymphocytes were sorted by FACS and allowed to rest for 2 days with human IL2. Resting T lymphocytes were then restimulated with plaque-bound antibodies to aCD3 and soluble CD28 for 24 hours.The cell supernatant was collected for ELISA analysis. Figure 6B shows gel assays of the PCR product amplified from the target genomic region. The arrow indicates the deletion in the target gRNA genomic region. Figure 6C shows qPCR assays of SIRPy expression after knockout. Significance is indicated as ****p < 0.0001, ***p < 0.0002, **p < 0.0021, *p < 0.0332, and ns p > 0.05 using the GraphPad Prism unpaired t-test. Error bars represent ± ETM. Figure 6D is a series of flow cytometry graphs showing the expression of human SIRPy in both CD4+ and CD8+ T lymphocytes after downregulation of SIRPy expression by CRISPR. Four days post-infection, the cells were centrifuged and stained with antibody to human SIRPy.Figure 6E shows the percentage of SIRPy+ cells in total CD4 or CD8 T lymphocytes after CRISPR suppression. Figure 6F shows an ELISA of human IFNγ in the cell supernatant from two independent experiments. Significance is indicated as ****p < 0.0001, ***p < 0.0002, **p < 0.0021, *p < 0.0332, and ns p > 0.05 using the two-way ANOVA test in GraphPad Prism. Error bars represent ± ETM. Figures 7A–7F demonstrate that SIRPy overexpression in Treg lymphocytes enhanced Treg suppressor function. Figure 7A is a series of FACS graphs and a histogram showing SIRPy expression in tumor-infiltrating lymphocytes from non-small cell lung cancer tissue. Figure 7B is a schematic diagram showing the experimental flow of SIRPy overexpression and Treg suppression assay. Treg lymphocytes were FACS-sorted from PanT cells isolated from human SCMs and activated using aCD3 / CD28 Dynabeads for 2 days. Activated Treg lymphocytes were transfected with retroviruses to overexpress SIRPy (RV-SIRPy) or infected with an RV vector lacking the SIRPy coding sequence as a control (RVVec).Five days post-infection by centrifugation, GFP+ Treg lymphocytes were sorted by FACS and allowed to stand overnight with human IL-2 (200 U / ml) before being added to the suppression assay. On the day of suppression assay preparation, responding CD4 T lymphocytes were isolated from sympathetic cellular ...Figure 7D is a series of flow cytometry graphs showing human FOXP3 expression in control Tregs or Tregs overexpressing SIRPy, classified by FACS. Figure 7E is a series of flow cytometry graphs showing CTV dilution in T lymphocytes mixed with SIRPy-overexpressing or control Tregs. Figure 7F is a graph showing the percentage of cell proliferation at different Treg-to-responder cell ratios. * indicates a p-value < 0.05 using a Student's t-test. Error bars represent ± ETM. Figures 8A–8F demonstrate that antibodies to SIRPy have nonspecific inhibitory effects on T cell proliferation. Figure 8A is a series of FACS plots showing the expression of SIRPy (left plot) and CD47 (right plot) on Jurkat T cells after CRISPR suppression of SIRPy (SIRPy KO), CD47 (CD47 KO), or both SIRPy and CD47 (DKO). Each panel shows the plot using either a matched isotype control antibody (sotype) or untransfected control cells (NT control). Figure 8B shows SIRPy-Fc and SIRPa-Fc protein binding assays on Jurkat T cells. All Fe fusion proteins were added at 5 pg / ml. The binding of fusion proteins to cells was detected by flow cytometry using a PE-conjugated human IgG anti-Fe. Figure 8C shows the study of the antagonistic activity of anti-SIRPy antibodies (LSB2).20 and 0X119) on SIRPyFc binding to Jurkat T lymphocytes. All IgG Fe proteins were added at 5 pg / ml and all antibodies were added at 10 pg / ml. An IgG antibody (IgGr) was used as a control. The binding of fusion proteins to cells was detected by flow cytometry using a PE-conjugated human IgG anti-Fe. Figure 8D is a graph showing counts per minute (CPM) of human panT cells isolated from healthy donors' SPCs stimulated with allogeneic dendritic cells (DCs) at a 10 T lymphocyte:1 DC ratio for 7 days. Antibodies were added on day 0 of culture at 10 pg / ml. T lymphocyte proliferation was measured by a conventional 3H-thymidine incorporation assay.Figure 8E is a graph showing the primary plasma cells (PPCs) of control T lymphocytes, SIRPy-suppressed panT cells, or CD47-suppressed panT cells stimulated with allogeneic dendritic cells (DCs) at a 10 T lymphocyte:1 DC ratio for 7 days. Antibodies were added on day 0 of culture at 10 pg / ml. T lymphocyte proliferation was measured using a conventional 3H-thymidine incorporation assay. Figure 8F shows human panT cells or CD8 T lymphocytes isolated from the primary plasma cells (PPCs) of healthy donors stimulated with different concentrations of plaque-bound anti-CD3 for 3 days. Antibodies against SIRPy or CD47 were added on day 0 of culture at 10 pg / ml. T lymphocyte proliferation was measured using a conventional 3H-thymidine incorporation assay. Figures 9A–9E demonstrate that the OX117 clone of the SIRPy antibody, which binds to a specific SIRPy epitope, enhances T cell proliferation and cytokine secretion. Figure 9A is a series of FACS graphs showing the binding of SIRPy antibodies to parental Jurkat T cells and SIRPy-overexpressing Jurkat T cells. Figure 9B shows that only the OX117 antibody modifies the binding of SIRPy-Fc proteins to Jurkat T cells. Jurkat T cells were pretreated with SIRPy antibodies at 10 pg / ml. SIRPy-Fc proteins were added at 10 pg / ml. The binding of the fusion proteins to the cells was detected by flow cytometry using PE-conjugated human IgG anti-Fe. Figures 9C and 9D show that the OX117 clone of the specific anti-SIRPy antibody has the strongest antagonistic activity on human panT cells, in stimulating proliferation and cytokine production.The plates were coated with SIRPy antibodies at 10 pg / ml. Human panT cells isolated from healthy donors' SCMs were stimulated with the CD3 / CD28 T cell activator ImmunoCult along with SIRPy antibodies bound to a plate for 3 days. In Figure 9C, T cell proliferation was measured using a conventional 3H-thymidine incorporation assay. Figure 9D shows a cytometric bead array (CBA) assay of human IFNγ in the cell supernatant of human panT cells stimulated for 48 hours. Figure 9E is an overview of the binding epitopes between SIRPy complexes: FabOX117 and between SIRPcc complexes: CD47, showing that CD47 and FabOX117 bind to different residues on SIRPy (Nettleship et al., BMC Structural Biology 13: 13 (2013)). Figure 10 provides a table summarizing the properties of commercial SIRPy antibodies and their functions in T lymphocytes. DETAILED DESCRIPTION SIRPF, SIRPF-BINDING MOLECULES AND SIRPF INHIBITORS Signaling regulatory protein gamma (SIRPy or SIRPG), also known as CD172g, SIRPB2, SIRP-B2, and bA77C3.1, is a member of the signaling regulatory protein (SIRP) family and belongs to the immunoglobulin (Ig) superfamily. Like other SIRP family members, SIRPy has three type I transmembrane glycoproteins, each comprising three Ig-like domains: an extracellular region, a single transmembrane domain, and a short cytoplasmic domain. Unlike other SIRP receptor family members, SIRPy lacks cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to recruit downstream signaling molecules to mediate cell signaling.SIRPy functions in the negative regulation of receptor tyrosine kinase-coupled signaling processes and in integrin-independent adhesion of lymphocytes to antigen-presenting cells. SIRPy is highly expressed in human blood, thymus, and splenic tissue. Within human SPCs, SIRPy is primarily expressed on activated T lymphocytes and natural killer (NK) cells. Additionally, several recent studies of tumor and adjacent tissue secRNA profiling have shown that SIRPy is highly expressed on T lymphocytes isolated from various tumors. Like SIRPa, SIRPy binds to CD47, although with lower affinity than SIRPa (Brooke et al., J Immunol 173(4): 2562-2570 (2004)). SIRPy and its role in the immune system are reviewed in van Beek et al., J Immunol 175(12): 7781-7787 (2005). The crystal structure of SIRPy is described in Nettleship et al., BMC Structural Biology 13: 13 (2013). The SIRPy gene is a polymorphic gene located on human chromosome 20 (p13 arm) and comprises 8 exons. Several SIRPy variants have been described in the human population, and the protein sequences of such SIRPy variants can be found on the National Center for Biotechnology Information (NCBI) website under the reference numbers NP_001034597.1 (precursor of isoform 3; SEQ ID NO: 1), NP_061026.2 (precursor of isoform 1; SEQ ID NO: 3), and NP_543006.2 (precursor of isoform 2; SEQ ID NO: 5). SIRPy messenger RNA (mRNA) sequences can be found on the NCBI website under reference number NM_001039508.1 (transcript variant 3; SEO ID NO: 2); reference number NM_018556.4 (transcript variant 1; SEO ID NO: 4) and reference number NM 080816.2 (transcript variant 2; SEQ ID NO: 6).Among the variants, a protective intron variant, rs2281808, within the SIRPy intron has been identified as associated with a decreased risk of developing type 1 diabetes (T1D) through several genome-wide association studies. A recent study of the rs2281808 intron variant indicated that the SNP variant resulted in reduced SIRPy expression on T lymphocytes. However, the biological activity of SIRPy remains largely unknown, partly due to the lack of a homologous gene in mice. Previous studies have shown that anti-SIRPy or anti-CD47 antibodies can inhibit T cell proliferation and IFN-γ secretion from T cells triggered by allogeneic immature CD4 cells in mixed lymphocyte reactions (Piccio et al., Blood, 105:2421-2427, 2005). However, in these earlier studies, the binding epitope of the anti-SIRPy antibody was unknown, and the mechanisms of its inhibitory effect on T cell proliferation were unclear. In such studies, it was unknown whether the antibody's blockade of the CD47-SIRPy interaction was the cause of the decreased T cell proliferation, and it was unclear whether SIRPy has additional biological functions beyond those involving its interaction with CD47. In example embodiments of the currently disclosed methods, a SIRPy-binding molecule is administered to a subject. As used herein, the term SIRPy-binding molecule refers to any compound or molecule that binds to SIRPy to form a SIRPy-binding interaction. For example, the SIRPy-binding molecule comprises or is a small molecular weight compound, an amino acid, a peptide, a polypeptide, a protein, a polymer, a carbohydrate, a lipid, a nucleic acid, an oligonucleotide, DNA, or RNA. Optionally, the SIRPy-binding molecule is a protein, such as, for example, an antigen-binding protein described herein. In some embodiments, the SIRPy-binding molecule is an antibody or an antigen-binding fragment thereof. In many cases, the binding interaction formed between SIRPy and the SIRPy-binding molecule is a non-covalent interaction. For example, the SIRPy-binding molecule can, in various ways, form ionic bonds, van der Waals interactions, hydrophobic interactions, and / or hydrogen bonds with one or more amino acid residues of SIRPy. ινΐΛ / a / zuz ι / ui Optionally, the non-covalent binding interaction is a reversible non-covalent binding interaction. The binding interaction can be described in terms of the Kd, the equilibrium dissociation constant, a ratio of kOff / kOn, between SIRPy and the SIRPy-binding molecule. The lower the Kd value of the SIRPy-binding molecule, the greater its affinity for SIRPy. For example, the Kd value of the SIRPy-binding molecule for SIRPy is micromolar, nanomolar, picomolar, or femtomolar. For example, the Kd of the antigen-binding proteins provided herein is within the range of approximately 10⁴ to 10⁶ M, 10⁷ to 10⁻¹² M, or 10¹³ to 10⁻¹⁵ M. In example aspects, the SIRPy-binding molecule binds to SIRPy with a Kd of approximately 0.01 nM at approximately 20 nM, 0.02 nM at 20 nM, 0.05 nM at 20 nM, 0.05 nM at 15 nM, 0.1 nM at 15 nM, 0.1 nM to 10 nM, 1 nM to 10 nM or 5 nM to 10 nM. In several cases, the SIRPy-binding molecule binds to D1 and / or the CD47-binding site of SIRPy. In several cases, the SIRPy-binding molecule binds to both D1 and Ig domain 2 (D2) of SIRPy. In some examples, the SIRPy-binding molecule binds to both D1 and D2, optionally at the interface between D1 and D2. Optionally, the SIRPy-binding molecule binds to the binding site of a SIRPy-binding partner other than CD47. Figure 9E illustrates SIRPy, its Ig domains, and the CD47-binding site. In some examples, the SIRPy-binding molecule binds to the epitope to which the SIRPy monoclonal antibody OX117 binds. In some embodiments, the SIRPy-binding molecule competes with a reference antibody known to bind to SIRPy (e.g., OX117) for SIRPy binding. In several cases, the SIRPy-binding molecule binds to SIRPy with the same or higher affinity than OX117.In some embodiments, the SIRPy-binding molecule is OX117, or an antigen-binding fragment thereof. Figure 9E illustrates the binding interaction between SIRPy and the antibody OX117 fab. The SIRPy-binding molecule forms hydrogen bonds with one or more of the amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPy. In some embodiments, the SIRPy-binding molecule forms hydrogen bonds with each of the amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPy. In some embodiments, the SIRPy-binding molecule binds to an epitope that does not overlap with the CD47-binding site. In example cases, after binding to SIRPy, the SIRPy-binding molecule enhances T cell activation, T cell proliferation, and cytokine secretion. In some cases, disclosure methods increase T cell activation, T cell proliferation, and cytokine secretion to any degree or level relative to a control.For example, in some respects, the increase provided by the disclosure methods is at least or about 1% to about 10% increase (for example, at least or about 1% increase, at least or about 2% increase, at least or about 3% increase, at least or about 4% increase, at least or about 5% increase, at least or about 6% increase, at least or about 7% increase, at least or about 8% increase, at least or about 9% increase, at least or about 9.5% increase, at least or about 9.8% increase, at least or about 10% increase) with respect to a control.In example embodiments, the increase provided by the disclosure methods is greater than 100%, for example, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or even 1000% compared to a control. In example embodiments, T lymphocyte activation, T lymphocyte proliferation, and cytokine secretion are increased at least or approximately 1.5-fold, at least or approximately 2.0-fold, at least or approximately 3.0-fold, at least or approximately 4.0-fold, at least or approximately 5.0-fold, at least or approximately 10.0-fold, at least or approximately 25-fold, at least or approximately 50-fold, at least or approximately 75-fold, or at least or approximately 100-fold or more, compared to a control. The control in various aspects is the activation of T lymphocytes, the proliferation of T lymphocytes and the secretion of cytokines without the SIRPy-binding molecule binding to SIRPy. In some examples, the SIRPy-binding molecule induces a conformational change in SIRPy upon binding. This conformational change can alter the accessibility of binding partner sites. It can also allow different binding partners to bind to SIRPy. Additionally, the conformational change can lead to dimerization or multimerization of SIRPy molecules. For example, dimerization or multimerization of SIRPy may prevent one or more binding partners from binding to SIRPy. Alternatively, dimerization or multimerization may enhance the binding of one or more binding partners to SIRPy. In some cases, the SIRPy-binding molecule may simultaneously bind to two SIRPy molecules or promote SIRPy dimerization. In some embodiments, the SIRPy-binding molecule blocks SIRPy function; for example, the SIRPy-binding molecule is a SIRPy inhibitor. Accordingly, in example embodiments of the currently disclosed methods, a SIRPy inhibitor is administered to a subject. As used herein, the term SIRPy inhibitor refers to any compound or molecule that reduces or inhibits SIRPy function. In example cases, the SIRPy inhibitor reduces the signal transduction that occurs after the binding of a SIRPy-binding partner to SIRPy. In various cases, the SIRPy inhibitor reduces a binding interaction between SIRPy and a SIRPy-binding partner. In various aspects, the SIRPy inhibitor reduces SIRPy expression in the subject's cells. In some embodiments, the SIRPy inhibitor binds to SIRPy. In other embodiments, the SIRPy inhibitor binds to a SIRPy binding partner. As used herein, the terms inhibit and reduce, and words derived from them, do not necessarily mean 100% or complete inhibition, elimination, or reduction. Rather, there are varying degrees of inhibition and / or reduction that those skilled in the art recognize as having a potentially beneficial or therapeutic effect. In this regard, the SIRPy inhibitors in this disclosure may reduce or inhibit SIRPy function to any degree or level.In example embodiments, the reduction or inhibition provided by the SIRPy inhibitor is at least or approximately 10% reduction or inhibition (e.g., at least or approximately 20% reduction or inhibition, at least or approximately 30% reduction or inhibition, at least or approximately 40% reduction or inhibition, at least or approximately 50% reduction or inhibition, at least or approximately 60% reduction or inhibition, at least or approximately 70% reduction or inhibition, at least or approximately 80% reduction or inhibition, at least or approximately 90% reduction or inhibition, at least or approximately 95% reduction or inhibition, at least or approximately 98% reduction or inhibition, at least or approximately 99% reduction or inhibition, or approximately 100% reduction or inhibition). In some examples, the SIRPy inhibitor reduces SIRPy expression in the subject's cells. In some cases, the SIRPy inhibitor reduces SIRPy expression on the cell surface of T lymphocytes. In some examples, the T lymphocytes are located within a tumor or tumor microenvironment. In some cases, the T lymphocytes are tumor-infiltrating T lymphocytes. In some examples, the T lymphocytes are regulatory T lymphocytes (Tregs). In some aspects, the T lymphocytes are depleted T lymphocytes, or optionally, depleted CD8+ T lymphocytes. Optionally, the T lymphocytes are memory lymphocytes. In some aspects, the memory lymphocytes are CD8+ memory lymphocytes or central CD4+ memory lymphocytes. In some examples, the SIRPy inhibitor is a molecule that targets a nucleic acid encoding SIRPy. In example cases, the SIRPy inhibitor is an antisense molecule that mediates RNA interference (RNA).RNA degradation is a ubiquitous mechanism of gene regulation in plants and animals in which target mRNAs are degraded in a sequence-specific manner (Sharp, Genes Dev., 15, 485-490 (2001); Hutvagner et al., Curr. Opin. Genet. Dev., 12, 225-232 (2002); Fire et al., Nature, 391, 806-811 (1998); Zamore et al., Cell, 101, 25-33 (2000)). The natural degradation process of RNA is initiated by the dsRNA-specific endonuclease Dicer, which promotes the cleavage of long dsRNA precursors into double-stranded fragments between 21 and 25 nucleotides long, called small interfering RNAs (snRNAs; also known as short interfering RNAs) (Zamore et al., Cell. 101, 25-33 (2000); Elbashiry et al., Genes Dev., 15, 188-200 (2001); Hammond et al., Nature, 404, 293-296 (2000); Bernstein et al., Nature, 409, 363-366 (2001)). siRNAs are incorporated into a large protein complex that recognizes and cleaves target mRNAs (Nykanen et al., Cell, 107, 309-321 (2001).The Dicer requirement for siRNA maturation in cells can be circumvented by introducing synthetic 21-nucleotide siRNA duplexes, which inhibit the expression of transfected and endogenous genes in a variety of mammalian cells (Elbashir et al., Nature, 411: 494-498 (2001)). For example, the SIRPy inhibitor mediates iRNA and in some cases is a specific siRNA molecule that inhibits the expression of the nucleic acid (e.g., mRNA) encoding the SIRPy protein. The term siRNA, as used herein, refers to an RNA (or RNA analog) comprising approximately 10 to approximately 50 nucleotides (or nucleotide analogs) that is capable of directing or mediating iRNA.In example embodiments, a siRNA molecule comprises approximately 15 to approximately 30 nucleotides (or nucleotide analogues) or approximately 20 to approximately 25 nucleotides (or nucleotide analogues), e.g., 21–23 nucleotides (or nucleotide analogues). siRNA can be double-stranded or single-stranded, preferably double-stranded. Alternatively, the SIRPy inhibitor is a short hairpin RNA (hRNA) molecule specifically designed to inhibit the expression of the nucleic acid (e.g., mRNA) that encodes the SIRPy protein. The term hRNA, as used herein, refers to a molecule of approximately 20 or more base pairs in which a single-stranded RNA partially contains a palindromic base sequence and forms a double-stranded structure within it (i.e., a hairpin structure). An hRNA may be a siRNA (or a siRNA analog) that folds into a hairpin structure.chRNAs typically comprise approximately 45 to 60 nucleotides, including the approximately 21-nucleotide sense and antisense hairpin portions, optional protrusions on the non-loop side approximately 2 to 6 nucleotides long, and the loop portion, which can be, for example, approximately 3 to 10 nucleotides long. chRNA can be chemically synthesized. Alternatively, chRNA can be produced by joining the sense and antisense strands of a DNA sequence in reverse directions and synthesizing RNA in vitro with T7 RNA polymerase using the DNA as a template. Although no specific theory or mechanism is desired, it is believed that after chRNA is introduced into a cell, it is degraded to a length of approximately 20 bases or more (e.g., representatively, 21, 22, or 23 bases), causing tRNA synthesis, which produces an inhibitory effect.Therefore, hRNA elicits RNA and can thus be used as an effective disclosure component. hRNA may preferably have a 3' protruding end. The length of the double-stranded portion is not particularly limited, but is preferably approximately 10 or more nucleotides, and more preferably approximately 20 or more nucleotides. In this case, the 3' protruding end may preferably be DNA, more preferably DNA at least 2 nucleotides long, and even more preferably DNA 2–4 nucleotides long. In terms of example, the SIRPy inhibitor is a microRNA (miRNA). As used herein, the term microRNA refers to a small (e.g., 15–22 nucleotides) non-coding RNA molecule that pairs its bases with mRNA molecules to silence gene expression by repressing translation or degrading the target. The microRNA and its therapeutic potential are described in the technique. See, for example, Mulligan, MicroRNA: Expression, Detection, and Therapeutic Strategies, Nova Science Publishers, Inc., Hauppauge, NY, 2011; Bader and Lammers, The Therapeutic Potential of microRNAs, Innovations in Pharmaceutical Technology, pp. 52–55 (March 2011). In one example, SIRPy inhibitors reduce signal transduction following the binding of a SIRPy binding partner to SIRPy. In several aspects, SIRPy inhibitors reduce signal transduction following the binding of CD47 to SIRPy, for example, signaling in endothelial cells induced by CD47-SIRPy binding interactions that leads to transendothelial T cell migration (Stefanidakis et al., Blood 112: 1280-1289 (2008)). In several aspects, SIRPy inhibitors reduce signal transduction following the binding of a SIRPy binding partner to the immunoglobulin D1 (D1) and / or immunoglobulin D2 (D2) domains of SIRPy. In one case, the SIRPy inhibitor reduces the signal transduction that occurs after the binding of a SIRPy binding partner to the interface between the immunoglobulin D1 domain and the immunoglobulin D2 domain of SIRPy.In several aspects, the SIRPy inhibitor enhances the secretion of IFNy by activated T lymphocytes. In several cases, the SIRPy inhibitor reduces a binding interaction between SIRPy and a SIRPy binding partner.In example aspects, the SIRPy inhibitor inhibits at least or approximately 10% of the binding interactions between SIRPy and the SIRPy binding partner (e.g., at least or approximately 20% of the binding interactions, at least or approximately 30% of the binding interactions, at least or approximately 40% of the binding interactions, at least or approximately 50% of the binding interactions, at least or approximately 60% of the binding interactions, at least or approximately 70% of the binding interactions, at least or approximately 80% of the binding interactions, at least or approximately 90% of the binding interactions, at least or approximately 95% of the binding interactions, at least or approximately 98% of the binding interactions, at least or approximately 99% of the binding interactions, or approximately 100% of the binding interactions).In other cases, the SIRPy binding partner binds to the interface between the immunoglobulin D1 domain and the immunoglobulin D2 domain of SIRPy. In several cases, the SIRPy binding partner is CD47. In various instances, the SIRPy binding partner binds to D1 and / or D2. In some ways, the SIRPy inhibitor is a soluble portion of SIRPy that binds to CD47 or another SIRPy binding partner. In some ways, the soluble portion of SIRPy is a decoy that, upon binding to CD47 or another SIRPy binding partner, leads to a null response, for example, a lack of SIRPy-CD47-mediated signaling. In some ways, the soluble portion of SIRPy comprises at least amino acids 29–360 of the SIRPy amino acid sequence. In some ways, the soluble portion of SIRPy comprises at least amino acids 29–360 of the human SIRPy amino acid sequence (SEQ ID NO: NP_061026.2). In some embodiments, the SIRPy inhibitor is a SIRPy-Fc that binds to CD47 or other SIRPy binding partners. In various respects, the SIRPy-Fc is a decoy that, by binding to CD47 or other SIRPy binding partners, leads to a null response, e.g., a lack of SIRPy-CD47-mediated signaling. In various respects, the SIRPy-Fc comprises at least amino acids 29–360 of the SIRPy amino acid sequence. In some embodiments, the SIRPy inhibitor is a CRISPR-linked RNA (gRNA). CRISPR suppression systems contain a guide RNA (gRNA) and a CRISPR-associated endonuclease (Cas protein). The term gRNA, as used herein, refers to a short RNA molecule of approximately 100 or more base pairs. The gRNA contains approximately 20 base pairs of nucleotide spacer and a scaffold sequence required for binding to the Cas protein. By altering the 20 base pairs toward the 5' end of the gRNA, the gRNA can be targeted to any genomic region complementary to that sequence. The 20-base-pair-long nucleotide spacer can be chemically synthesized and paired with the scaffold RNA to form a gRNA in vitro. The full length of a gRNA can be chemically synthesized in vitro. Alternatively, the gRNA can be produced using viral vectors that target the U6 RNA polymerase III promoter.The desired 20-base-pair target sequence immediately precedes a protospacer adjacent motif (PAM). The RNA gene guides the Cas nuclease to the target sequence by complementary base pairing, and the Cas nuclease mediates a double-strand break a few nucleotides upstream of the PAM. Target cells will use non-homologous end joining (NHEJ) or homology-directed repair (HDR) to repair the double-strand break. In many cases, NHEJ causes deletions, insertions, or frameshift mutations in the target DNA region, resulting in a knockout mutation of the target gene. In some ways, the SIRPy inhibitor is a soluble portion of CD47 that binds to SIRPy. In some ways, the soluble portion of CD47 is a decoy that, upon binding to SIRPy, leads to a null response, for example, a lack of SIRPy-CD47-mediated signaling. In some ways, the soluble portion of CD47 comprises at least amino acids 26-133 of the human CD47 amino acid sequence. ANTIGEN-BINDING PROTEINS In example cases, the SIRPy-binding molecule, for instance, the SIRPy inhibitor, is an antigen-binding protein that binds to SIRPy. In other examples, the SIRPy inhibitor is an antigen-binding protein that binds to SIRPy or to SIRPy's binding partner (for example, CD47). The antigen-binding protein, in various respects, is an antibody, an antigen-binding antibody fragment, or an antibody protein product. As used herein, the term antibody refers to a protein having a known immunoglobulin structure, comprising heavy and light chains, and comprising variable and constant regions.For example, an antibody might be an IgG, which is a Y-shaped structure of two identical pairs of polypeptide chains, each pair having a light chain (typically with a molecular weight of approximately 25 kDa) and a heavy chain (typically with a molecular weight of approximately 50–70 kDa). An antibody has variable and constant regions. In IgG formulations, the variable region is generally approximately 100–110 or more amino acids long, comprises three complement-determining regions (CDRs), is primarily responsible for antigen recognition, and varies substantially among different antibodies that bind to different antigens. The constant region allows the antibody to recruit cells and molecules of the immune system.The variable region consists of the N-terminus regions of each light and heavy chain, while the constant region consists of the C-terminus portions of each of the heavy and light chains. (Janeway et al., Structure of the Antibody Molecule and the Immunoglobulin Genes, Immunobiology: The Immune System in Health and Disease, 4th ed. Elsevier Science Ltd. / Garland Publishing, (1999)). ινΐΛ / a / zuz ι / ui The general structure and properties of antibody CDRs have been described in the technique. In summary, within an antibody scaffold, CDRs are embedded within heavy- and light-chain variable regions, where they constitute the regions largely responsible for antigen binding and recognition. A variable region typically comprises at least three heavy- or light-chain CDRs (Kabat et al., 1991, Sequences of Proteins of Immunological Interest, Public Health Service NIH, Bethesda, Md.; see also Chothia and Lesk, 1987, J. Mol. Biol. 196:901-917; Chothia et al., 1989, Nature 342: 877-883), within a conserved scaffold region (designated conserved scaffold regions 1-4, FR1, FR2, FR3, and FR4, by Kabat et al., 1991; see also Chothia and Lesk, 1987, supra). Antibodies can comprise any constant region known to the art. Human light chains are classified as kappa and lambda light chains. Heavy chains are classified as mu, delta, gamma, alpha, or epsilon and define the antibody isotype as IgM, IgD, IgG, IgA, and IgE, respectively. IgG has several subclasses, including, but not limited to, IgG1, IgG2, IgG3, and IgG4. IgM has subclasses, including, but not limited to, IgG1 and IgG2. The embodiments described herein include all of these antibody classes or isotypes. The light chain constant region can be, for example, a human lambda or kappa light chain constant region.The heavy chain constant region can be, for example, alpha, delta, epsilon, gamma, or mu heavy chain constant regions, such as a human alpha, delta, epsilon, gamma, or mu heavy chain constant region. Therefore, in example embodiments, the antibody is an isotype antibody of IgA, IgD, IgE, IgG, or IgM, including any one of IgG1, IgG2, IgG3, or IgG4. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. The antibody can be a monoclonal or polyclonal antibody. In some embodiments, the antibody comprises a sequence that is substantially similar to a naturally occurring antibody produced by a mammal, such as a mouse, rabbit, goat, horse, chicken, hamster, human, and the like. In this respect, the antibody can be considered a mammalian antibody, such as a mouse antibody, rabbit antibody, goat antibody, horse antibody, chicken antibody, hamster antibody, human antibody, and the like. In certain respects, the antibody is a human antibody. In certain respects, the antibody is a chimeric antibody or a humanized antibody. The term chimeric antibody refers to an antibody that contains domains from two or more different antibodies.A chimeric antibody may, for example, contain the constant domains of one species and the variable domains of a second, or more generally, it may contain stretches of amino acid sequence from at least two species. A chimeric antibody may also contain domains from two or more different antibodies within the same species. The term humanized, when used in relation to antibodies, refers to antibodies that have at least CDR regions from a non-human source that are technically engineered to have a structure and immunological function more similar to true human antibodies than the antibodies of the original source. For example, humanization may involve grafting a CDR from a non-human antibody, such as a mouse antibody, into a human antibody. Humanization may also involve selecting amino acid substitutions to make a non-human sequence more similar to a human sequence. An antibody can be cleaved into fragments by enzymes such as papain and pepsin. Papain cleaves an antibody to produce two Fab fragments and a single Fe fragment. Pepsin cleaves an antibody to produce an αF(ab')2 fragment and a pFc' fragment. In the example aspects of this disclosure, the antigen-binding protein is either an antigen-binding fragment or an antibody. As used herein, the term antigen-binding antibody fragment refers to a portion of an antibody that can bind to the antibody's antigen and is also known as the antigen-binding fragment or antigen-binding portion. In example cases, the antigen-binding antibody fragment is either a Fab fragment or an F(ab')2 fragment. In several respects, the antigen-binding protein is an antibody protein product. As used herein, the term antibody protein product refers to any one of several antibody alternatives that in various cases are based on the architecture of an antibody but are not found in nature. In some respects, the antibody protein product has a molecular weight within the range of at least approximately 12–150 kDa. In certain respects, the antibody protein product has a valency range (n) from monomeric (n = 1), to dimeric (n = 2), to trimeric (n = 3), to tetrameric (n = 4), or higher-order valency.Antibody protein products, in some respects, are those based on the complete antibody structure and / or those that mimic antibody fragments that retain full antigen-binding capacity, e.g., scFv, Fab and VHH / VH (discussed below). The smallest antigen-binding antibody fragment that retains its entire antigen-binding site is the Fv fragment, which consists entirely of variable (V) regions. A flexible, soluble amino acid peptide linker is used to connect the V regions to an scFv (single-stranded variable fragment) for molecule stabilization, or constant (C) domains are added to the V regions to generate a Fab (fragment, antigen-binding) fragment. Both scFv and Fab fragments can be readily produced in host cells, such as prokaryotic host cells. Other protein antibody products include disulfide-stabilized scFv (ds-scFv), single-stranded Fab (scFab), as well as di- and multimeric antibody formats such as di-, tria-, and tetrabodies, or minibodies (the miniAbs) comprising various formats consisting of scFv linked to oligomerization domains.The smallest fragments are camelid heavy-chain antibody VHH / VH fragments, as well as single-domain antibodies (sdAbs). The most frequently used building block for creating novel antibody formats is the single-stranded variable (V) domain antibody fragment (scFv), which comprises heavy- and light-chain V domains (VH and VL domains) linked by a peptide bond of approximately 15 amino acid residues. A peptibody, or peptide-Fc fusion, is another protein antibody product. The structure of a peptibody consists of a biologically active peptide grafted onto an Fe domain. Peptibodies are well described in the art. See, for example, Shimamoto et al., mAbs 4(5): 586–591 (2012). Other protein antibody products include a single-chain antibody (SCA), a diabody, a tribody, a tetrabody, bispecific or nonspecific antibodies, and the like. Bispecific antibodies can be divided into five main classes: BsIgG, attached IgG, BsAb fragments, bispecific fusion proteins, and BsAb conjugates. See, for example, Spiess et al., Molecular Immunology 67(2) Part A: 97-106 (2015). In terms of examples, the antigen-binding protein is a bispecific T-cell ligand molecule (BiTE®). BiTE® molecules are fusion proteins comprising two scFvs from different antibodies. One binds to CD3, and the other binds to a target antigen. BiTE® molecules are known in the art. See, for example, Hueñis et al., Immuno Cell Biol 93(3): 290-296 (2015); Rossi et al., MAbs 6(2): 381-91 (2014); Ross et al., PLoS One 12(8): e0183390. In several ways, the antigen-binding protein (e.g., an antibody or an antigen-binding fragment thereof) binds to a SIRPy. The antigen-binding protein binds to SIRPy in some ways in a non-covalent and reversible manner. In example embodiments, the binding strength of antigen-binding proteins can be described in terms of their affinity, a measure of the strength of the interaction between the SIRPy binding site and its binding partner. In example embodiments, antigen-binding proteins with high affinity for SIRPy will bind a larger amount of SIRPy in a shorter period of time than low-affinity antigen-binding proteins. In example embodiments, antigen-binding proteins with low affinity for SIRPy will bind a smaller amount of SIRPy over a longer period of time than high-affinity antigen-binding proteins.In terms of example, antigen-binding proteins have an equilibrium association constant, KA, which is at least 105M-1, at least ινΐΛ / a / zuz ι / u i. 106M'1, at least 107M'1, at least 108M-1, at least 109M-1 or at least 1010M-1. As the skilled worker will understand, KA can be influenced by factors including pH, temperature and buffer composition. In example embodiments, the binding strength of the antigen-binding protein (e.g., an antibody or an antigen-binding fragment thereof) to SIRPy can be described in terms of its sensitivity. Kd is the equilibrium dissociation constant, a ratio of kOff / kon, between the antigen-binding protein and SIRPy. Kd and KA are inversely proportional. The value of Kd is related to the concentration of the antigen-binding protein (the amount of antigen-binding protein required for a particular experiment); the lower the Kd value (lower concentration required), the greater the affinity of the antigen-binding protein. In example aspects, the binding strength of the antigen-binding protein to SIRPy can be described in terms of KD.For example, the d of antigen-binding proteins is approximately 10⁻¹M, approximately 10⁻²M, approximately 10⁻³M, approximately 10⁻⁴M, approximately 10⁻⁵M, approximately 10⁻⁶M, or less. For example, the Kd of the antigen-binding protein is micromolar, nanomolar, picomolar, or femtomolar. For example, the Kd of the antigen-binding proteins is within a range of approximately 10⁻⁴ to 10⁻⁶M, or 10⁻⁷ to 10⁻⁹M, or 10⁻¹⁰ to 10⁻¹²M, or 10⁻¹³ to 10⁻¹⁵M. For example, the antigen-binding protein binds to human SIRPy with a Kd greater than, or approximately, 0.04 nM. In example aspects, the antigen-binding protein binds to human SIRPy with a Kd of approximately 0.01 nM to approximately 20 nM, 0.02 nM to 20 nM, 0.05 nM to 20 nM, 0.05 nM to 15 nM, 0.1 nM to 15 nM, 0.1 nM to 10 nM, 1 nM to 10 nM or 5 nM to 10 nM.In several respects, the KD is lower than the KD that SIRPy has for CD47, optionally less than approximately 23 μM. Optionally, the antigen-binding protein comprises a fully human antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, or a chimeric antibody or antigen-binding fragment thereof. The antigen-binding protein may also comprise a Fab, Fab', F(ab')2, or single-chain Fv. In various respects, the SIRPy inhibitor comprises one, two, three, four, five, or more of the complementarity-determining regions (CDRs) of the heavy and light chains of an anti-SIRPy antibody. In certain aspects, the antigen-binding protein binds to an epitope on SIRPy, optionally where the epitope is located within, near, or at a site other than the CD47-binding site of SIRPy. In various aspects, the antigen-binding protein binds to an epitope comprising the amino acid sequence SLLPVGP (SEQ ID NO: 21; iviA / a / zuz ι / ui amino acids 29-35 of the amino acid sequence of SIRPy, LTKRNNMDF (SEQ ID NO: 22) and KFRKGS (SEQ ID NO: 23). For example, the antigen-binding protein comprises a fully human antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a chimeric antibody or antigen-binding fragment thereof, or a Fab, Fab', F(ab')2, or single-stranded Fv, which competes with a reference antibody, a reference antibody known to bind SIRPy (e.g., 0X117), for SIRPy binding. For example, the antigen-binding protein binds to an epitope to which the reference antibody (e.g., 0X117) binds. For example, the antigen-binding protein has a Kd for SIRPy that is similar to or equal to the Kd of the reference antibody (e.g., 0X117).In example, the antigen-binding protein has a KD for SIRPy that is lower than the KD of the reference antibody (e.g., 0X117) and therefore has a higher affinity for SIRPy compared to the reference antibody. The appropriate techniques for determining the binding affinity of an antigen-binding protein to a ligand or target are known in the art and include, for example, surface plasmon resonance (SPR)-based methods, flow cytometry-based methods, or fluorescence microscopy, the KinExA® method (see, for example, International Patent Application Publication No. WO2019140196, Azimzadeh and Regenmortel, J Mol Recognit 3(3): 108-116 (1990); Schuck et al., Curr Protoc Cell Biol Chapter 17: Unit 17.6 (2004); Tseng et al., Electrophoresis 23(6): 836-846 (2002); Van Regenmortel et al., Immunol Invest 26(1-2): 67-82 (1997)). In example cases, the antigen-binding protein that competes with a reference antibody (e.g., OX117) for binding to SIRPy reduces the amount of anti-SIRPy antibody (e.g., OX117) bound to SIRPy in an in vitro competitive binding assay.In illustrative terms, the amount of reference antibody (e.g., 0X117) bound to SIRPy in the presence of the antigen-binding protein of the present disclosure is reduced by at least or about 25%, at least or about 30%, at least or about 35%, at least or about 40%, at least or about 45%, at least or about 50%, at least or about 55%, at least or about 60%, at least or about 65%, at least or about 70%, at least or about 75%, at least or about 80%, at least or about 85%, at least or about 90% or more (e.g., at least or about 95%, at least or about 98%).In several aspects, the antigen-binding proteins of this disclosure inhibit the binding interaction between SIRPy and the reference antibody, and this inhibition is characterized by an IC50 of less than approximately 250 nM. Specifically, the antigen-binding proteins exhibit IC50 values ​​of less than approximately 200 nM, less than approximately 150 nM, less than approximately 100 nM, less than approximately 50 nM, less than approximately 25 nM, less than approximately 10 nM, less than approximately 5 nM, less than approximately 1 nM, less than 0.5 nM, or less than 0.1 nM. A suitable competitive binding assay that can be used to determine the reduced amount of reference antibody (e.g., OX117) bound to SIRPy comprises the steps of incubating the reference antibody (e.g., OX117) with SIRPy or SIRPy-expressing cells in the presence of a currently disclosed antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that competes with the reference antibody (e.g., OX117) for binding to SIRPy. The amount of reference antibody (e.g., OX117) bound to SIRPy is measured with and without the currently disclosed antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that competes for binding to SIRPy. In several instances, the antigen-binding proteins of this disclosure compete with the reference antibody for binding to SIRPy and, therefore, reduce the amount of SIRPy bound to the reference antibody as determined by a FACS-based assay in which the fluorescence of a fluorophore-conjugated secondary antibody that binds to the Fe of the reference antibody is measured in the absence or presence of a particular amount of the antigen-binding protein of this disclosure. In several aspects, the FACS-based assay is performed with the reference antibody, the fluorophore-conjugated secondary antibody, and cells expressing SIRPy. In several aspects, the cells are genetically engineered to overexpress SIRPy. In some aspects, the cells are HEK293T cells transduced with a viral vector to express SIRPy. In other aspects, the cells express SIRPy endogenously.Before the FACS-based assay is performed, in some respects, cells that endogenously express SIRPy are predetermined as either cells with low SIRPy expression or cells with high SIRPy expression. In the art, other binding assays are known, for example, competitive binding assays or competition assays, which test the ability of an antibody to compete with another antigen-binding protein for binding to an antigen or an epitope thereof. For example, suitable receptor-ligand competition assays are described in International Patent Application No. WO2019140196, incorporated herein by reference. See, for example, Trikha et al., Int J Cancer 110: 326 335 (2004); Tam etal., Circulation 98(11): 1085-1091 (1998); publicación de solicitud de patente de EE.UU. N.° US20140178905, Chand et al., Biologicals 46: 168-171 (2017); Liu et al., Anal Biochem 525: 89-91 (2017); Goolia et al., J Vet Diagn Invest 29(2): 250-253 (2017); Hunter y Cochran, Methods Enzymol 250: 21-44 (2016); Cox et al., Immunoassay Methods, Immunoassay Methods. 1 de mayo de 2012 [Actualizado el 8 de julio de 2019], En: Sittampalam GS, Grossman A, Brimacombe K, et al., editores. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004Disponible de: https: / / www.ncbi.nlm.nih.gov / books / NBK92434 / ; Clarke, William, Immunoassays for Therapeutic Drug Monitoring and Clinical Toxicology, Handbook of Analytical Separations, Volumen 5, páginas 95-112 (2004) y Goolia et al., J Vet Diagn Invest 29(2): 250-253 (2017).In example aspects, the SIRPy-binding molecule competes with OX117 for SIRPy binding as determined by any of the assays described in these references. CANCER TREATMENT This disclosure provides methods for treating a subject with a tumor or cancer. In example embodiments, the cancer treatment method comprises administering to the subject a SIRPy-binding molecule (e.g., an antibody or an antigen-binding fragment thereof) in an amount effective to treat a tumor or cancer in the subject. In some embodiments, the SIRPy-binding molecule is a SIRPy inhibitor. In some embodiments, the cancer treatment method comprises administering to the subject an antigen-binding protein (e.g., an antibody or an antigen-binding fragment thereof) that binds to a SIRPy epitope in an amount effective to treat a tumor or cancer in the subject. Any of the antigen-binding proteins that bind to an epitope on SIRPy (e.g., SIRPy-binding molecules and SIRPy-inhibitors) discussed herein may be used in such methods. In certain embodiments, the SIRPy-binding molecule or SIRPy-inhibitor (e.g., an antibody or antigen-binding fragment thereof) binds to an epitope on SIRPy. In some embodiments, the SIRPy epitope is located within, near, or at a site other than the CD47-binding site of SIRPy. In several respects, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) binds to an epitope comprising the amino acid sequence of SLLPVGP (SEQ ID NO: 21; amino acids 29-35 of the SIRPy amino acid sequence, LTKRNNMDF (SEQ ID NO: 22) and KFRKGS (SEQ ID NO: 23). In several cases, the SIRPy-binding molecule binds to D1 and / or the CD47-binding site of SIRPy. In several cases, the SIRPy-binding molecule binds to both the D1 and Ig domains (D2) of SIRPy. For example, the SIRPy-binding molecule binds to both iviA / a / zuz i / ui oyor D1 as well as D2, optionally at the interface between D1 and D2. Optionally, the SIRPy-binding molecule binds to the binding site of a SIRPy-binding partner other than CD47. Figure 9E provides an illustration of SIRPy, its Ig domains, and the CD47-binding site. In example cases, the SIRPy-binding molecule binds to the epitope to which the SIRPy monoclonal antibody 0X117 binds, optionally where the SIRPy-binding molecule competes with a reference antibody known to bind SIRPy (e.g., 0X117) for SIRPy binding. In some embodiments, the SIRPy-binding molecule competes with 0X117 for SIRPy binding. In various cases, the SIRPy-binding molecule binds to SIRPy with the same or higher affinity than 0X117. In some embodiments, the SIRPy-binding molecule is 0X117 or an antigen-binding fragment thereof. Figure 9E provides an illustration of the binding interaction between SIRPy and the fab of antibody 0X117.The SIRPy-binding molecule in various aspects forms hydrogen bonds with one or more of the amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPy. The SIRPy-binding molecule in various aspects forms hydrogen bonds with each of the amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPy. Optionally, the SIRPy-binding molecule binds to an epitope that does not overlap with the CD47-binding site. In example cases, after binding to SIRPy, the SIRPy-binding molecule enhances T cell activation, T cell proliferation, and cytokine secretion. In some cases, disclosure methods increase T cell activation, T cell proliferation, and cytokine secretion to any degree or level, compared to a control.For example, in some respects, the increase provided by the disclosure methods is at least or about 1% to about 10% increase (e.g., at least or about 1% increase, at least or about 2% increase, at least or about 3% increase, at least or about 4% increase, at least or about 5% increase, at least or about 6% increase, at least or about 7% increase, at least or about 8% increase, at least or about 9% increase, at least or about 9.5% increase, at least or about 9.8% increase, at least or about 10% increase), with respect to a control. In example realizations, the increase provided by the disclosure methods is greater than 100%, for example, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900% or even 1000%, with respect to a control.In example realizations, T cell activation, T cell proliferation, and cytokine secretion are increased at least or approximately 1.5-fold, at least or approximately 2.0-fold, at least or approximately 3.0-fold, at least or approximately 4.0-fold, at least or approximately 5.0-fold, at least or approximately 10.0-fold, at least or approximately 25-fold, at least or approximately 50-fold, at least or approximately 75-fold, at least or approximately 100-fold, or more, compared to a control. The control is T cell activation, T cell proliferation, and cytokine secretion without the SIRPy-binding molecule binding to SIRPy. In some cases, the SIRPy-binding molecule induces a conformational change in SIRPy upon binding. This conformational change can, in some instances, alter the accessibility of the binding sites of other binding partners. Alternatively, the conformational change may allow different binding partners to bind to SIRPy. Additionally, the conformational change may induce dimerization or multimerization of SIRPy molecules. In some instances, dimerization or multimerization of SIRPy may prevent one or more binding partners from binding to SIRPy. In other instances, dimerization or multimerization of SIRPy may enhance the binding of one or more binding partners to SIRPy. In some cases, the SIRPy-binding molecule may simultaneously bind to two SIRPy molecules or promote SIRPy dimerization. As used herein, the term "treat," as well as related terms, does not necessarily imply 100% or complete treatment. Instead, there are varying degrees of treatment that a person skilled in the art recognizes as having a potential benefit or therapeutic effect. In this sense, the cancer treatment methods in this disclosure may provide any amount or any level of treatment. Additionally, the treatment provided by the methods in this disclosure may include the treatment of one or more conditions, symptoms, or signs of the cancer being treated. Treatment provided by the methods in this disclosure may also include slowing the progression of the cancer.For example, methods may treat cancer by increasing T-cell activity (e.g., T-cell effector activity) or by enhancing an immune response against the tumor or cancer, reducing tumor or cancer growth or tumor burden, reducing tumor cell metastasis, increasing tumor or cancer cell death or tumor regression, reducing T-cell suppressor activity, and the like. Accordingly, methods for increasing T-cell effector activity or reducing T-cell suppressor activity in a subject with a tumor or cancer are provided herein. In example embodiments, the method comprises administering a SIRP inhibitor to the subject in an amount effective to increase effector activity or reduce suppressor activity in the subject.Furthermore, in accordance with the above, methods for enhancing an immune response against a tumor or cancer in a subject are provided herein. In example embodiments, the method comprises administering a SIRP inhibitor to the subject in an amount effective to enhance an immune response against a tumor or cancer. In various aspects, the methods treat by delaying the onset or recurrence of cancer by at least 1 day, 2 days, 4 days, 6 days, 8 days, 10 days, 15 days, 30 days, two months, 3 months, 4 months, 6 months, 1 year, 2 years, 3 years, 4 years, or more. In various aspects, the methods treat by increasing the subject's survival. In some examples, the methods in this disclosure provide treatment by delaying the occurrence or onset of metastasis. In some cases, the methods provide treatment by delaying the occurrence or onset of a new metastasis. PHARMACEUTICAL COMPOSITIONS, ROUTES AND TIMES OF ADMINISTRATION OF THE SIRPF-BINDING MOLECULE The following embodiments disclose pharmaceutical compositions, routes, and timing of administration of the antigen-binding proteins (e.g., an antibody or antigen-binding fragment thereof) of the present invention that bind to SIRPy. In some embodiments, the antigen-binding protein is either a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof). In some embodiments, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is administered to a subject as part of a pharmaceutical composition. In other embodiments, the pharmaceutical composition comprises a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) or a pharmaceutically acceptable salt thereof that binds to SIRPy. In various aspects, the pharmaceutically acceptable salt of the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is prepared in situ during the final isolation and purification of the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy, or it is prepared separately by reacting a free base function with a suitable acid.Examples of acids that can be used to form pharmaceutically acceptable acid addition salts include, for example, an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, and an organic acid, such as oxalic acid, maleic acid, succinic acid, and citric acid. Acid addition salts in various forms include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphor sulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate (isothionate), lactate, maleate, methanesulfonate, nicotinate, and others. 2-naphthalenesulfonate, oxalate, palmitoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, ptoluenesulfonate and undecanoate. In many respects, the pharmaceutically acceptable salt of the SIRPy-binding molecule or SIRPy-inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is a base-addition salt. Base-addition salts can also be prepared in situ during the final isolation and purification of the SIRPy-binding molecule or SIRPy-inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy, or by reacting a carboxylic acid-containing fraction with a suitable base such as the hydroxide, carbonate, or bicarbonate of a pharmaceutically acceptable metal cation, or with ammonia or a primary, secondary, or tertiary organic amine.In many cases, the pharmaceutically acceptable salt of the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is an alkali metal or alkaline earth metal-based cation such as lithium, sodium, potassium, calcium, magnesium, and aluminum salts, and the like, and non-toxic quaternary ammonia and amine cations including ammonium, tetramethylammonium, tetraethylammonium, methylammonium, dimethylammonium, trimethylammonium, triethylammonium, diethylammonium, and ethylammonium, among others. Other representative organic amines useful for the formation of base-addition salts include, for example, ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine, and the like.Furthermore, basic nitrogen-containing groups can be quaternized with SIRPy inhibitors such as lower alkyl halides like methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; long-chain halides like decyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides; arylalkyl halides like benzyl and phenethyl bromides; and others. This yields products that are either water-soluble or oil-dispersible. In several respects, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy using currently disclosed methods is formulated with a pharmaceutically acceptable carrier, diluent, or excipient prior to administration to the subject. Depending on the route of administration and other factors, the specific SIRPy binder or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy may be mixed with one or more additional pharmaceutically acceptable drugs or ingredients, including, for example, acidifying agents, additives, adsorbents, aerosol propellants, air-displacing agents, alkalizing agents, anti-caking agents, anticoagulants, antimicrobial preservatives, antioxidants, antiseptics, bases, binders, buffering agents, chelating agents, and coating agents.iviA / a / ¿u¿ ι / ui coloring agents, desiccants, detergents, diluents, disinfectants, disintegrants, dispersing agents, dissolution enhancers, colorants, emollients, emulsifying agents, emulsion stabilizers, fillers, film-forming agents, flavor enhancers, flavoring agents, flow enhancers, gelling agents, granulating agents, humectants, lubricants, mucoadhesives, ointment bases, ointments, oily vehicles, organic bases, lozenge bases, pigments, plasticizers, brightening agents, preservatives, sequestering agents, skin penetrants, solubilizing agents, solvents, stabilizing agents, suppository bases, surfactants, surfactants, suspending agents, sweetening agents, therapeutic agents, thickening agents, tonicity agents, toxicity agents, viscosity-increasing agents, water-absorbing agents, water-miscible cosolventswater softeners or wetting agents. The SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy according to the currently disclosed methods can be administered to the subject by any suitable route of administration. For example, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy can be administered to a subject by parenteral, nasal, oral, pulmonary, topical, vaginal, or rectal administration. The following analysis of routes of administration is provided simply to illustrate exemplary embodiments and should not be construed as limiting the scope of the invention in any way. By way of example, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy using currently disclosed methods is formulated for parenteral administration. The term parenteral means not through the digestive tract but by another route, such as subcutaneous, intramuscular, intrathecal, or intravenous. Suitable formulations for parenteral administration include sterile aqueous and non-aqueous isotonic solutions for injection that may contain antioxidants, buffers, bacteriostatic agents, and solutes that provide isotonicity to the formulation with the blood of the intended recipient; and sterile aqueous and non-aqueous suspensions that may include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. The SIRPy-binding molecule or SIRPy inhibitor (e.g.,an antibody or antigen-binding fragment thereof) that binds to SIRP and can be administered with a physiologically acceptable diluent in a pharmaceutical carrier, such as a sterile liquid or a mixture of liquids, including water, saline solution, aqueous dextrose and related sugar solutions, an alcohol such as ethanol or hexadecyl alcohol, a glycol such as propylene glycol or polyethylene glycol, dimethyl sulfoxide, glycerol, ketals such as 2,2-dimethyl-153-dioxolane-4-methanol, ethers, poly(ethylene glycol) 400, oils, fatty acids, esters or glycerides of fatty acids or glycerides of acetylated fatty acids with or without the addition of a pharmaceutically acceptable surfactant such as a soap or detergent, a suspending agent such as pectin, carbomers, methylcellulose, hydroxypropylmethylcellulose or carboxymethylcellulose,or emulsifying agents and other pharmaceutical adjuvants. Oils that may be used in parenteral formulations include petrolatum, and animal, vegetable, or synthetic oils. Specific examples of oils include peanut, soybean, sesame, cottonseed, corn, olive, petrolatum, and mineral oil. Fatty acids suitable for use in parenteral formulations include oleic acid, stearic acid, and isostearic acid. Ethyl oleate and isopropyl myristate are examples of suitable fatty acid esters. For example, the formulation for parenteral administration includes a soap. Soaps suitable for use in parenteral formulations include fatty alkali metal salts, ammonium, and triethanolamine, and suitable detergents include (a) cationic detergents such as, for example, dimethyl dialkyl ammonium halides and alkylpyridinium halides, (b) anionic detergents such as, for example,alkyl, aryl, and olefin sulfonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates, (c) nonionic detergents such as, for example, fatty amine oxides, fatty acid alkanolamides, and polyoxyethylene polypropylene copolymers, (d) amphoteric detergents such as, for example, alkyl-p-aminopropionates and quaternary ammonium salts of 2-alkylimidazoline, and (e) mixtures thereof. In example cases, preservatives and buffers are present in the parenteral formulation. To minimize or eliminate irritation at the injection site, such compositions may contain one or more nonionic surfactants with a hydrophilic-lipophilic (HLB) equilibrium.The abbreviated form stands for Hydrophile-Lipophile Balance, ranging from approximately 12 to approximately 17. The amount of surfactant in such formulations typically ranges from approximately 5% to approximately 15% by weight. Suitable surfactants include polyethylene glycol sorbitan fatty acid esters, such as sorbitan monooleate, and high molecular weight adducts of ethylene oxide with a hydrophobic base, formed by the condensation of propylene oxide with propylene glycol. Parenteral formulations are, in some respects, presented in sealed single-dose or multi-dose containers, such as ampoules, vials, and syringes, and can be stored in a cryo-dried (lyophilized) state, requiring only the addition of a sterile liquid excipient, for example, water for injection, immediately before use. Extemporaneous injectable solutions and suspensions are, in some respects, prepared from sterile powders.granules and tablets of the type previously described. By way of example, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is formulated for injection. The injectable formulations are in compliance with this disclosure. The requirements for effective pharmaceutical carriers for injectable compositions are known to those skilled in the art (see, for example, Pharmaceutics and Pharmacy Practica, J.B. Lippincott Company, Philadelphia, PA, Banker and Chalmers, eds., pp. 238–250 (1982), and ASHP Handbook on Injectable Drugs, Toissel, 4th ed., pp. 622–630 (1986)). Optionally, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is administered to the subject via subcutaneous injection. In various cases, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is administered orally to the subject. Suitable formulations for oral administration may consist of (a) liquid solutions, such as an effective amount of the analogue of this disclosure dissolved in diluents such as water, saline solution, or orange juice; (b) capsules, sachets, tablets, lozenges, and lozenges, each containing a predetermined amount of the active ingredient, as solids or granules; (c) powders; (d) suspensions in a suitable liquid; and (e) suitable emulsions. Liquid formulations may include diluents such as water and alcohols, e.g., ethanol, benzyl alcohol, and polyethylene alcohols, with or without the addition of a pharmaceutically acceptable surfactant.Capsule forms may be of the common soft or hard gelatin type containing, for example, surfactants, lubricants, and inert fillers such as lactose, sucrose, calcium phosphate, and corn starch. Tablet forms may include one or more of lactose, sucrose, mannitol, corn starch, potato starch, alginic acid, microcrystalline cellulose, gum arabic, gelatin, guar gum, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate, calcium stearate, zinc stearate, stearic acid, and other excipients, colorants, diluents, buffering agents, disintegrating agents, wetting agents, preservatives, flavoring agents, and pharmacologically compatible excipients.Lozenge forms may comprise the analogue of the present disclosure in a flavor, usually sucrose and gum arabic or tragacanth, as well as lozenges comprising the analogue of the present disclosure in an inert base, such as gelatin and glycerin, or sucrose and gum arabic, emulsions, gels, and the like containing, in addition, such excipients that are known in the art. The SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy can be administered according to any regimen, including, for example, daily (once a day, twice a day, three times a day, four times a day, five times a day, six times a day), three times a week, twice a week, every two days, every three days, every four days, every five days, every six days, every week, every two weeks, every three weeks, monthly, or bimonthly. DOSAGES The following embodiments disclose dosages of the antigen-binding proteins (e.g., an antibody or antigen-binding fragment thereof) of the present invention that bind to SIRPy. In some embodiments, the antigen-binding protein is either a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof). The SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is believed to be useful in methods of increasing effector activity or reducing suppressive activity of T lymphocytes or increasing an immune response against a tumor or cancer in a subject, as described herein, and is therefore believed to be useful in methods of treating or preventing one or more diseases, e.g., cancer. The amount or dose of the SIRPy-binding molecule or SIRPy inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy administered should be sufficient to produce, e.g., a therapeutic or prophylactic response in the subject or animal for a reasonable period of time.For example, the dose of the SIRPy-binding molecule or SIRPy inhibitor, or the antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy (e.g., a SIRPy inhibitor), should be sufficient to treat the cancer within approximately 1 to 4 days, or approximately 1 to approximately 4 weeks or more (e.g., approximately 5 to approximately 20 weeks or more) from the time of administration. In certain embodiments, the time period could be even longer. The dose will be determined by the efficacy of the particular active agent and the condition of the animal (e.g., a human), as well as by the body weight of the animal (e.g., a human) being treated. Many assays for determining an administered dose are known in the art. For the purposes of this document, an assay comprising comparing the secretion of IFNγ by activated T lymphocytes following the administration of a given dose of a SIRPγ-binding molecule or SIRPγ inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPγ to a mammal among a group of mammals, each group receiving a different dose, could be used to determine a starting dose to be administered to a mammal in a clinical trial. Methods for measuring IFNγ secretion by activated T lymphocytes are known in the art and are described herein. ινΐΛ / a / zuz ι / υ i The dose of the SIRPy-binding molecule or SIRPy inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy will also be determined by the existence, nature, and extent of any adverse side effects that may accompany the administration of a particular active agent.Typically, the attending physician will determine the dosage of the SIRPy-binding molecule, SIRPy inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) to be used to treat each individual patient, taking into account a variety of factors, such as age, body weight, general health, diet, sex, the specific SIRPy-binding molecule, SIRPy inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) to be administered, the route of administration, and the severity of the condition being treated. By way of example, and without intending to limit this disclosure, the dosage of the SIRPy-binding molecule, SIRPy inhibitor, or antigen-binding protein (e.g., an antibody or antigen-binding fragment thereof) of currently disclosed methods may be approximately 0.0.0001 to approximately 1 g / kg of body weight of the subject being treated / day, from approximately 0.0001 to approximately 0.001 g / kg of body weight / day, or from approximately 0.01 mg to approximately 1 g / kg of body weight / day. CONTROLLED-RELEASE FORMULATIONS The following embodiments disclose controlled-release formulations of the antigen-binding proteins (e.g., an antibody or antigen-binding fragment thereof) of the present invention that bind to SIRPy. In some embodiments, the antigen-binding protein is either a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof). In some embodiments, the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy described herein may be modified into a slow-release form, so that the manner in which the active agent is released into the administered organism is controlled with respect to time and location within the organism (see, e.g., U.S. Patent No. 4,450,150).Slow-release forms of the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy may be, for example, an implantable composition comprising the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) and a porous or non-porous material, such as a polymer, wherein the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) is encapsulated in or diffuses through the material and / or through degradation of the non-porous material. The slow-release form is then implanted at the desired location within the subject's body, and the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy is released from the implant at a predetermined rate. In several respects, the pharmaceutical composition comprising the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy can be modified to have any type of in vivo release profile. In some respects, the pharmaceutical composition is an immediate-release, controlled-release, sustained-release, prolonged-release, delayed-release, or biphasic-release formulation. Methods for formulating peptides for controlled release are known in the art. See, for example, Qian et al., J Pharm 374: 46-52 (2009) and International Patent Application Publications No. WO 2008 / 130158, WO2004 / 033036; WO2000 / 032218; and WO 1999 / 040942. In various cases, the pharmaceutical composition comprising the SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy may further comprise, for example, micelles or liposomes, or some other encapsulated form, for storage and / or prolonged delivery effect. COMBINATIONS The following embodiments disclose combinations of the antigen-binding proteins (e.g., an antibody or antigen-binding fragment thereof) of the present invention that bind to SIRPy. In some embodiments, the antigen-binding protein is either a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof). In some cases, the SIRPy-binding molecule or SIRPy inhibitor that binds to SIRPy is administered to the subject alone, for example, without any additional active pharmaceutical ingredient. In other cases, the SIRPy-binding molecule or SIRPy inhibitor (for example, an antibody or antigen-binding fragment thereof) that binds to SIRPy is administered to the subject in combination with a chemotherapeutic agent. Chemotherapeutic agents suitable for use in the currently disclosed methods are known in the art and include, but are not limited to, platinum coordination compounds, topoisomerase inhibitors, antibiotics, antimitotic alkaloids, and difluoronucleosides, as described in U.S. Patent No. 6,630,124. In some embodiments, the chemotherapeutic agent is a platinum coordination compound; the term "platinum coordination compound" refers to any compound that inhibits tumor cell growth and provides platinum in ionic form. In some embodiments, the platinum coordination compound is cis-diaminodiaquoplatinum(II) ion. chloride chloride(diethylenediamine-platinum (II); dichloro(ethylenediamine)platinum (II), diammina(1,1-cyclobutanedicarboxylate) platinum (II) (carboplatin); spiroplatinum; proplatinum; diammina(2-ethylmalonate)-platinum (II); aqua(1,2-diaminod¡clohexane)-sulfatoplatán (II); (1,2-diam¡nocyclohexane)malonatoplat¡no (II); (1,2-diam¡noc¡clohexane)cis(pyruvate)platinum (II); (1,2-diaminocyclohexane)oxalatoplatone (II); ormaplatinum; and tetraplatinum. In some embodiments, cisplatin is the platinum coordination compound employed in the compositions and methods of the present invention. Cisplatin is commercially available under the name PLATINOL™ from Bristol Myers Squibb Corporation and is available as a powder for reconstitution with water, sterile saline solution, or another suitable vehicle. Other platinum coordination compounds suitable for use in the present invention are known and commercially available and / or can be prepared by known techniques. Cisplatin, or cis-dichlorodiamineplatin II, has been used successfully for many years as a chemotherapeutic agent in the treatment of various human solid malignant tumors. More recently, other diaminoplatin complexes have also shown efficacy as chemotherapeutic agents in the treatment of various human solid malignant tumors.These diaminoplatin complexes include, but are not limited to, spiroplatin and carboplatin. Although cisplatin and other diaminoplatin complexes have been widely used as chemotherapeutic agents in humans, they have had to be administered at high dosage levels, which can lead to toxicity problems such as kidney damage. In some embodiments, the chemotherapeutic agent is a topoisomerase inhibitor. Topoisomerases are enzymes capable of altering the topology of DNA in eukaryotic cells. Topoisomerases are fundamental for cellular functions and cell proliferation. Generally speaking, there are two classes of topoisomerases in eukaryotic cells: type I and type II. Topoisomerase I is a monomeric enzyme with a molecular weight of approximately 100,000. The enzyme binds to DNA and introduces a transient single-strand break, unwinds the double helix (or allows it to unwind), and then re-seals the break before dissociating from the DNA strand. The clinical efficacy of various topoisomerase inhibitors has been demonstrated in the treatment of humans with ovarian cancer, breast cancer, esophageal cancer, or non-small cell lung cancer. In some respects, the topoisomerase inhibitor is camptothecin or a camptothecin analogue. Camptothecin is a water-insoluble, cytotoxic alkaloid produced by the trees Camptotheca acuminata, native to China, and Nothapodytes foetida, native to India. Camptothecin inhibits the growth of various tumor cells. Compounds in the camptothecin analogue class are typically specific inhibitors of DNA topoisomerase I. Compounds in the camptothecin analogue class include, but are not limited to, topotecan, irinotecan, and 9-aminocamptothecin. In further embodiments, the chemotherapeutic agent is any camptothecin analogue that inhibits the growth of tumor cells claimed or described in: U.S. Patent No. 5,004,758, issued April 2, 1991, and European Patent Application No. 88311366.4, published June 21, 1989, as Publication No. 20 EP 0 321 122; U.S. Patent No. 4,604,463, issued August 5, 1986, and European Patent Application Publication No. EP 0 137 145, published April 17, 1985; U.S. Patent No. 4,473,692, issued on September 25, 1984, and European Patent Application Publication No. EP 0 074 256, published on March 16, 1983; U.S. Patent No.No. 4,545,880, issued on October 8, 1985 and European patent application publication number EP 0 074 256, published on March 16, 1983; European patent application publication number EP 0 088 642, published on September 14, 1983; Wani et al., J. Med. Chem., 29, 2358-2363 (1986); Nitta et al., Proc. 14th International Congress of Chemotherapy, Kyoto, 1985, Tokyo Press, Anticancer Section 1, pp. 28-30, especially a compound called CPT-11. CPT-11 is a camptothecin analogue with a 4-(piperidino)-piperidine side chain linked via a carbamate bond at C-10 of 10-hydroxy-7-ethyl camptothecin. Clinical trials in humans are currently underway with CPT-11, also referred to as irinotecan; Wani et al., J. Med. Chem., 23, 554 (1980); Wani et al., J. Med. Chem., 30, 1774 (1987); U.S. Patent No. 4,342,776, issued August 3, 1982; U.S. Patent Application No.581,916, filed on September 13, 1990 and European patent application publication number EP 418 099, published on March 20, 1991; U.S. patent no. 4,513,138, issued on April 23, 1985 and European patent application publication number EP 0 074 770, published on March 23, 1983; U.S. patent no. 4,399,276, issued on August 16, 1983 and European patent application publication number 0 056 692, published on July 28, 1982; full disclosure of each of which is incorporated herein by reference. All the compounds listed above from the camptothecin analogue class are commercially available and / or can be prepared using known techniques, including those described in the references listed above. The topoisomerase inhibitor can be selected from the group consisting of topotecan, irinotecan, and 9-aminocamptothecin. The preparation of numerous compounds of the camptothecin analogue class (including pharmaceutically acceptable salts, hydrates, and solvates thereof), as well as the preparation of oral and parenteral pharmaceutical compositions comprising such compounds of the camptothecin analogue class and a pharmaceutically acceptable inert carrier or diluent, are extensively described in U.S. Patent No. 5,004,758, issued April 2, 1991, and European Patent Application No. 88311366.4, published June 21, 1989, as Publication No. EP 0 321 122, the teachings of which are incorporated herein by reference. In other embodiments, the chemotherapeutic agent is an antibiotic compound. Suitable antibiotics include, but are not limited to, doxorubicin, mitomycin, bleomycin, daunorubicin, and streptozocin. In some embodiments, the chemotherapeutic agent is an antimitotic alkaloid. Antimitotic alkaloids can generally be extracted from Cantharanthus roseus and have been shown to be effective as chemotherapeutic agents against cancer. A large number of semisynthetic derivatives have been studied both chemically and pharmacologically (see O. Van Tellingen et al., Anticancer Research, 12, 1699-1716 (1992)). The antimitotic alkaloids of the present invention include, but are not limited to, vinblastine, vincristine, vindesine, paclitaxel (PTX; Taxol®), and vinorelbine. The latter two antimitotic alkaloids are commercially available from Eli Lilly and Company and Pierre Fabre Laboratories, respectively (see U.S. Patent No. 5,620,985). In one exemplary aspect of the present invention, the antimitotic alkaloid is vinorelbine. In other embodiments of the invention, the chemotherapeutic agent is a difluoronucleoside. It is known in the art that 2'-deoxy-2',2'-difluoronucleosides have antiviral activity. These compounds are disclosed and taught in U.S. Patent Nos. 4,526,988 and 4,808,614. European Patent Application 184,365 discloses that these same difluoronucleosides have oncolytic activity. In certain specific aspects, the 2'-deoxy-2',2'-difluoronucleoside used in the compositions and methods of the present invention is 2'-deoxy-2',2'-difluoroctidine hydrochloride, also known as gemcitabine hydrochloride. Gemcitabine is commercially available or can be synthesized in a multi-step process as disclosed and taught in U.S. Patent Nos. 4,526,988, 4,808,614 and 5,223,608, the teachings of which are incorporated herein by reference. In some examples, the chemotherapeutic agent is a hormonal therapy agent. Examples of hormonal therapy agents include letrozole, tamoxifen, bazedoxifene, exemestane, leuprolide, goserelin, fulvestrant, anastrozole, and toremifene. In some examples, the hormonal therapy agent is a luteinizing hormone (LH) blocker, such as gosarelin, or an LH-releasing hormone (LRH) agonist. In some examples, the hormonal therapy agent is an ER-targeting agent (e.g., fulvestrant). IVIA / a / ZUZ l / UI or tamoxifen), rapamycin, a rapamycin analog (e.g., everolimus, temsirólimus, ridaforolimus, zotarólimus, and 32-deoxo-rapamycin), an anti-HER2 drug (e.g., trastuzumab, pertuzumab, lapatinib, T-DM1, or neratinib), or a PI3K inhibitor (e.g., taselisib, alpelisib or buparlisib). In terms of example, the chemotherapeutic agent is a CDK4 / 6 inhibitor, such as palbociclib, ribociclib, or abemaciclib (see, for example, Knudsen and Witkiewicz, Trends Cancer 3(1): 39-55 (2017)). SUBJECTS In the example realizations of this disclosure, the subject is a mammal, including, but not limited to, mammals of the order Rodentia, such as mice and hamsters, and mammals of the order Logomorpha, such as rabbits; mammals of the order Carnivora, including felines (cats) and canines (dogs); mammals of the order Artiodactyla, including bovines (cows) and porcines (pigs); or of the order Perssodactyla, including equines (horses). In some respects, the mammals are of the order Primates, Ceboidea, or Simioidea (monkeys), or of the order Anthropoidea (humans and apes). In some respects, the mammal is a human being. For example, the subject has cancer or a tumor. In some respects, cancer is a selected one from the group consisting of acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal or anorectal area, eye cancer, cancer of the intrahepatic bile ducts, joint cancer, cancer of the neck, gallbladder or pleura, cancer of the nose, nasal cavity or middle ear, cancer of the oral cavity, vulvar cancer, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, Hodgkin lymphoma, hypopharyngeal cancer, kidney cancer, laryngeal cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharyngeal cancer, non-Hodgkin lymphoma, ovarian cancer, pancreatic cancer, mesentery cancer, omentum and peritoneum, pharyngeal cancer,Prostate cancer, rectal cancer, kidney cancer (e.g., renal cell carcinoma (RCC)), small bowel cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, ureter cancer, and bladder cancer. In specific instances, the cancer is selected from the group consisting of: head and neck cancer, ovarian cancer, cervical cancer, bladder and esophageal cancer, pancreatic cancer, gastrointestinal cancer, gastric cancer, breast cancer, endometrial and colorectal cancer, hepatocellular carcinoma, glioblastoma, bladder cancer, lung cancer (e.g., non-small cell lung cancer (NSCLC)), and bronchioloalveolar carcinoma. In specific instances, the tumor is non-small cell lung cancer (NSCLC), head and neck cancer, kidney cancer, triple-negative breast cancer, or gastric cancer. In example aspects, the subject has a tumor (for example, a solid tumor, a hematological malignancy, or a lymphoid malignancy),and the pharmaceutical composition is administered to the subject in an effective amount to treat the tumor. In other example aspects, the tumor is non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck cancer, kidney cancer, breast cancer, melanoma, ovarian cancer, liver cancer, pancreatic cancer, colon cancer, prostate cancer, gastric cancer, lymphoma, or leukemia, and the pharmaceutical composition is administered to the subject in an effective amount to treat the tumor. Optionally, the subject has hepatocellular carcinoma (HCC), colorectal cancer (CRC), lung cancer, optionally, non-small cell lung cancer (NSCLC). RELIEF FROM IMMUNE SUPPRESSION AND ENHANCEMENT OF THE IMMUNE RESPONSE Without being tied to any particular theory, the antigen-binding protein (e.g., an antibody or an antigen-binding fragment thereof) that binds to SIRPy described herein is useful for increasing the effector activity or reducing the suppressor activity of T lymphocytes. In some embodiments, the antigen-binding protein is either a SIRPy-binding molecule or a SIRPy-inhibitor. Furthermore, it is postulated that the SIRPy-binding molecules or SIRPy-inhibitors (e.g., an antibody or an antigen-binding fragment thereof) that bind to SIRPy described herein are useful for enhancing an immune response against a tumor or cancer. Accordingly, this disclosure provides methods for increasing the effector activity or reducing the suppressor activity of T lymphocytes in a subject with a tumor or cancer.In example embodiments, the method comprises administering to the subject an antigen-binding protein (e.g., an antibody or an antigen-binding fragment thereof) that binds to SIRPy in an amount effective to increase effector activity or reduce suppressor activity in the subject. In some embodiments, the antigen-binding protein is a SIRPy-binding molecule or a SIRPy inhibitor. Furthermore, this disclosure provides methods for enhancing an immune response against a tumor or cancer in a subject. In example embodiments, the method comprises administering to the subject a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or an antigen-binding fragment thereof) that binds to SIRPy in an amount effective to enhance an immune response against a tumor or cancer. The increase in effector activity of T lymphocytes provided by the methods in this disclosure may be at least or approximately 1% to approximately 10% increase (e.g., at least or approximately 1% increase, at least or approximately 2% increase, at least or approximately 3% increase, at least or approximately 4% increase, at least or approximately 5% increase, at least or approximately 6% increase, at least or approximately 7% increase, at least or approximately 8% increase, at least or approximately 9% increase, at least or approximately 9.5% increase, at least or approximately 9.8% increase, at least or approximately 10% increase) relative to a control.The increase in T lymphocyte effector activity provided by the methods in this disclosure may be at least or about 10% to more than about 95% increase (e.g., at least or about 10% increase, at least or about 20% increase, at least or about 30% increase, at least or about 40% increase, at least or about 50% increase, at least or about 60% increase, at least or about 70% increase, at least or about 80% increase, at least or about 90% increase, at least or about 95% increase, at least or about 98% increase, at least or about 99% increase, or about 100% increase) relative to a control.In example aspects, the control is a cancer or tumor or a subject or population of subjects that was not treated with the currently disclosed SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy or where the subject or population of subjects was treated with a placebo. The increase in an immune response provided by the methods in this disclosure may be at least or about 1% to about 10% increase (e.g., at least or about 1% increase, at least or about 2% increase, at least or about 3% increase, at least or about 4% increase, at least or about 5% increase, at least or about 6% increase, at least or about 7% increase, at least or about 8% increase, at least or about 9% increase, at least or about 9.5% increase, at least or about 9.8% increase, at least or about 10% increase) relative to a control.The increase in an immune response against a tumor or cancer provided by the methods in this disclosure may be at least or about 10% to more than about 95% increase (e.g., at least or about 10% increase, at least or about 20%, at least or about 30% increase, at least or about 40% increase, at least or about 50% increase, at least or about 60% increase, at least or about 70% increase, at least or about 80% increase, at least or about 90% increase, at least or about 95% increase, at least or about 98% increase, at least or about 99% increase, or about 100% increase) relative to a control.In example aspects, the control is a cancer or tumor or a subject or population of subjects that was not treated with the currently disclosed SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy or where the subject or population of subjects was treated with a placebo. The reduction in T lymphocyte suppressive activity provided by the methods in this disclosure may be at least or approximately 1% to approximately 10% reduction (e.g., at least or approximately 1% reduction, at least or approximately 2% reduction, at least or approximately 3% reduction, at least or approximately 4% reduction, at least or approximately 5% reduction, at least or approximately 6% reduction, at least or approximately 7% reduction, at least or approximately 8% reduction, at least or approximately 9% reduction, at least or approximately 9.5% reduction, at least or approximately 9.8% reduction, at least or approximately 10% reduction) relative to a control.The reduction in T-cell suppressive activity provided by the methods in this disclosure may be at least or approximately 10% to more than 95% reduction (e.g., at least or approximately 10% reduction, at least or approximately 20% reduction, at least or approximately 30% reduction, at least or approximately 40% reduction, at least or approximately 50% reduction, at least or approximately 60% reduction, at least or approximately 70% reduction, at least or approximately 80% reduction, at least or approximately 90% reduction, at least or approximately 95% reduction, at least or approximately 98% reduction, at least or approximately 99% reduction, or approximately 100% reduction) relative to a control.In example aspects, the control is a cancer or tumor or a subject or population of subjects that was not treated with the currently disclosed SIRPy-binding molecule or SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy or where the subject or population of subjects was treated with a placebo. Regarding methods to increase effector activity or reduce suppressor activity of T lymphocytes, T lymphocytes are, in various respects, located within a tumor or tumor microenvironment; optionally, T lymphocytes are tumor-infiltrating T lymphocytes. In some respects, T lymphocytes are regulatory T lymphocytes (Tregs). In various respects, T lymphocytes are exhausted T lymphocytes; optionally, exhausted CD8+ T lymphocytes. iviA / a / ¿u¿ ι / υ i osó / In certain cases, T lymphocytes are memory lymphocytes; optionally, memory lymphocytes are CD8+ memory lymphocytes or central CD4+ memory lymphocytes. Regarding methods for enhancing an immune response against a tumor or cancer, the immune response is mediated by T lymphocytes in many respects. T lymphocytes may be located within a tumor or tumor microenvironment. In some cases, these T lymphocytes are tumor-infiltrating T lymphocytes. In some cases, these T lymphocytes are regulatory T lymphocytes (Tregs). In some cases, these T lymphocytes are exhausted T lymphocytes, or optionally, exhausted CD8+ T lymphocytes. In certain cases, these T lymphocytes are memory lymphocytes; optionally, these memory lymphocytes are CD8+ memory lymphocytes or central CD4+ memory lymphocytes. By way of example, the subject of the currently disclosed method of increasing effector activity or reducing suppressor activity of T lymphocytes, or the currently disclosed method of enhancing an immune response against a tumor or cancer, is a subject as described herein. In various respects, the subject has a tumor or cancer. Optionally, the subject has hepatocellular carcinoma (HCC), colorectal cancer (CRC), lung cancer, optionally non-small cell lung cancer (NSCLC), or breast cancer. Without being tied to any particular theory, increased effector activity or reduced suppressor activity of T lymphocytes and / or enhanced immune responses against a tumor or cancer in a subject lead to the treatment of that tumor or cancer. Accordingly, this disclosure further provides methods for treating a subject with a tumor or cancer. In example embodiments, the method comprises increasing the effector activity or reducing the suppressor activity of T lymphocytes in the subject and / or enhancing an immune response against the tumor or cancer in the subject.The considerations and details of the treatment methods described above, which comprise administering to the subject a SIRPy-binding molecule or a SIRPy inhibitor (e.g., an antibody or antigen-binding fragment thereof) that binds to SIRPy, apply to the treatment methods described now (comprising increasing effector activity or reducing suppressive activity of T lymphocytes in the subject and / or increasing an immune response against the tumor or cancer in the subject). The following examples are provided simply to illustrate the present invention and in no way to limit its scope. EXAMPLES The studies described below confirm the T-cell-specific SIRPy expression pattern in humans. Although most T cells express SIRPy at high levels, interestingly, CD8 memory T cells and tumor-infiltrated CD8 depletion cells showed increased SIRPy expression compared to other T cells. Previous studies characterizing CD8 tumor-infiltrating lymphocytes (TILs) from breast tumors and melanoma tumor tissues suggest that tumor CD8 TILs are predominantly memory effector cells. The high SIRPy expression pattern in memory and depletion T cells suggests that SIRPy may negatively affect T cell effector function within the tumor environment.Interestingly, the in vitro functional data presented here are consistent with this hypothesis and confirm that SIRPy is a negative regulator of T lymphocyte effector function. Additionally, SIRPy enhances the suppressor function of Tregs. These data provide insights into the potential therapeutic intervention of targeting SIRPy in both T lymphocytes and Tregs to improve the immune response against tumors. EXAMPLE 1 The following example describes the materials and methods used in the Examples. Cell preparation and MACS microbead sorting: Small cell fragments (SCFs) were isolated from healthy donor blood samples using a Ficoll Hypaque density gradient (GE Healthcare Biosciences, Pittsburg, PA). CD8+ T cells and PanT cells were isolated from SCFs using Miltenyi negative selection microbead kits (Nos. 130-096-535 and 130-096-495, Miltenyi) according to the manufacturer's instructions. To isolate human regulatory T cells, CD4+ T cells were isolated from SCFs using the Human CD4+ T Cell Isolation Kit (130-096-533, Miltenyi) followed by enrichment of CD25+ T cells with CD25 microbeads (130-092-983, Miltenyi) according to the manufacturer's protocol. Finally, human regulatory T lymphocytes CD4+CD25+CD127- were classified by FACS. The classified panT cells, CD8 lymphocytes, and Treg cells were subjected to downstream function assays. In vitro induction of CD8 depletion: Purified human CD8 T lymphocytes were seeded at 1–2 x 10⁶ cells / ml and subjected to anti-CD3 (UCHT1, 0.2 pg / ml, BD Biosciences) and anti-CD28 (CD28.2, 2 pg / ml, BD Biosciences) stimulation for 3–4 days. The CD8 T lymphocytes were restimulated every 3–4 days with anti-CD3 (UCHT1, 1 pg / ml, BD Biosciences) and anti-CD28 (CD28.2, 2 pg / ml, BD Biosciences). The cells underwent restimulation at least twice as described above. Antibody staining by flow cytometry: The anti-human antibodies used for analysis by multicolor flow cytometry included: CD3 (Biolegend, 344804), CD4 (Biolegend, 300520), CD8 (Biolegend, 301040), SIRPy (Biolegend, 336606), mouse IgG1 isotype K control (Biolegend, 400112), CD14 (BD Biosciences, 558121), CD56 (Biolegend, 318321), CD45RA (Biolegend, 304112), CCR7 (Biolegend, 353232), CD127 (Biolegend, iviA / a / zuz ι / ui 351318), Foxp3 (Biolegend, 320214). CMSP samples were washed with MACS buffer and stained with fluorescently labeled anti-human antibodies. For intracellular Foxp3 staining, cells were fixed with an intracellular fixation and permeabilization buffer set (eBioscience, 00-5523-00) and stained with antibody for Foxp3. Flow cytometry data were acquired at LSRII using the FACSDiva software (Becton Dickinson). Data were analyzed using Flow Jo (TreeStar, Ashland, OR). SIRPy overexpression, T-cell restimulation, and cytokine detection: To overexpress human SIRPy in human T cells, human SIRPy was cloned into the MSCV-IRES-EGFP retroviral vector. The retrovirus was generated using the pAmpho packaging system (Clontech, No. 631530) before infecting the T cells. For T-cell infection, pan-T cells were isolated from human MSCV-IRES-EGFP using the Miltenyi Human Pan-T Cell Isolation Kit and activated with Dynabeads Human T-Activator CD3 / CD28 (ThermoFisher Scientific, No. 11131D) in a 1:1 ratio for 72 hours. 72 hours later, the Dynabeads were removed and the activated T lymphocytes were infected by centrifugation with retrovirus at 2000 rpm for 1 hour at 32 degrees. On day 5 post-infection by retrovirus centrifugation, GFP+ human SIRPy-overexpressing T lymphocytes were sorted by FACS and allowed to rest with human IL2 for 2 days. Equal amounts of control T lymphocytes or CD8 or CD4 human SIRPy-overexpressing T lymphocytes were seeded into 96 round-bottom wells and restimulated with plate-bound anti-CD3 (0.5 pg / ml) and anti-CD28 (1 pg / ml) (eBioscience 16-0037-85 and 160289-85). Cell supernatant was collected 24 hours after restimulation, and human IFNγ was measured by ELISA (eBioscience, 88-7316-88). CRISPR suppression in undifferentiated T lymphocytes: For CRISPR suppression in undifferentiated T lymphocytes, a crRNA-tracrRNA duplex was prepared by mixing equimolar concentrations of Alt-R crRNA and Alt-R tracrRNA (IDT) oligonucleotides. The mixed oligos were paired by heating at 95 °C for 5 min in a PCR thermocycler, and the mixture was slowly cooled to room temperature. Three crRNA-tracrRNA duplexes (3 pl, equivalent to 150 pmol each, total of 9 pl) and 6 μL (equivalent to 180 pmol) of TrueCut Cas9 Protein v2 (catalog number A36499; Thermo Fisher Scientific, 5 pg / ml) were gently mixed by pipetting and incubated at room temperature for 10–20 min. 200 μL of complete T lymphocyte medium were pre-warmed per well of a 96-well plate. 1-2 million T lymphocytes were resuspended in 20 μL of primary cell nucleofection solution (P2 Primary Cell 4D-Nucleofector X kit S [32 RCT, V4XP-2032; Lonza]).T lymphocytes were mixed and incubated with 15 µl of RNP at room temperature for 2 min in a 96-well round-bottom plate. The cell / RNP mixture was transferred to Nucleofection cuvette strips (4D-Nucleofector X kit S; Lonza). The cells were electroporated using a 4D nucleofector. The pulse for undifferentiated human T lymphocyte populations is EH100. After nucleofection, pre-warmed T lymphocyte medium was used to transfer the transfected cells to 96-well plates. Resting human T lymphocytes were cultured at 1 x 10⁶ per well in 200 µl of complete T lymphocyte medium for 3–5 days (containing IL-2 and IL-7). The decreases in expression were checked by iviA / a / zuz ι / u i. FACS in D5 after electroporation. The following were used in the study RNA targeting sequences: RNAcrl of SIRPy: 5'- GGGACCCGTCCTGTGGTTCAG-3' ' (SEQ ID NO: 7), RNAcrl2 of SIRPy: 5'- AAAAGGGAGCCCTGAGAACG-3' (SEQ ID NO: 8), RNAcrl3 of SIRPy: 5'- GTATGTGCCGACATCTGCTG-3' (SEQ ID NO: 9), RNAcrl of CD47: 5'- TACGTAAAGTGGAAATTTAA-3' (SEQ ID NO: 10), RNAcrl2 of CD47: 5'- TTTGCACTACTAAAGTCAGT-3' (SEQ ID NO: 11), RNAcrl3 of CD47: 5'- TCCATATTAGTAACAAAGCA-3' (SEQ ID NO: 12), RNAcrl of PD1: 5'- GCAGTTGTGTGACACGGAAG-3' (SEQ ID NO: 13), RNAcrl2 of PD1: 5'- GGGCCCTGACCACGCTCATG-3' (SEQ ID NO: 14), ARNcr3 de PD1: 5- GATCTGCGCCTTGGGGGCCA-3' (SEQ ID NO: 15). CRISPR suppression in activated T cells and Jurkat T cells: Human panT cells were activated with Dynabeads Human T-Activator CD3 / CD28 (ThermoFisher Scientific, No. 11131D) in a 1:1 ratio for 48 hours. After 48 hours, the Dynabeads were removed, and 100,000–200,000 activated T cells were resuspended in 20 µL of primary cell nucleofection solution (P2 Primary Cell 4D-Nucleofector X kit S [32 RCT, V4XP2032; Lonza]) and mixed with the RNP complex. The cell / RNP mixture was transferred to Nucleofection cuvette strips (4D-Nucleofector X kit S; Lonza). The cells were electroporated using a 4D nucleofector. The pulse for activated human T lymphocyte populations is CM138. After nucleofection, pre-warmed T lymphocyte medium was used to transfer the transfected cells to 96-well plates.Human T lymphocytes were cultured at 1 x 10⁵ per well in 200 μL of complete T lymphocyte medium (with IL-2). Decreases in expression were verified by FACS on day 2 after electroporation. For Jurkat T cell suppression, 200,000 Jurkat T cells were resuspended in 20 µL of primary cell nucleofection solution (P4 Primary Cell 4D-Nucleofector X kit S [32 RCT, V4XP-4032; Lonza]) and mixed with the RNP complex. The cell / RNP mixture was transferred to Nucleofection cuvette strips (4D-NucleofectorX kit S; Lonza). The cells were electroporated using a 4D nucleofector with the CM138 program. On day 3 after electroporation, the suppressed T cells were classified by FACS based on cell surface protein expression and further expanded for future experiments. Restimulation of suppressed T lymphocytes: On day 3 post-CRISPR suppression, T lymphocytes were restimulated, and SIRPy-CD4 or CD8+ T lymphocytes were sorted by FACS on day 4 post-CRISPR suppression. Sorted SIRPy-suppressed T lymphocytes were rested with human IL-2 for 2 days. Equal amounts of control T lymphocytes or human SIRPy-suppressed CD8+ or CD4+ T lymphocytes were seeded in 96 round-bottom wells and restimulated with anti-CD3 (0.5 pg / ml) and anti-CD28 (1 pg / ml). Cell supernatant was collected 24 hours after restimulation, and human IFN-γ was measured by ELISA. Real-time PCR: For qRT-PCR, total RNA was isolated from control or SIRPy-classified T lymphocytes that were restimulated 9 days after CRISPR / Cas9 delivery using the RNeasy Mini kit (Qiagen) according to the manufacturer's instructions. cDNA was reverse transcribed from these RNAs using the SuperScript IV First-Strand Synthesis System (No. 18091050, Invitrogen), and qRT-PCR was performed using QuantStudio3 (Applied Biosystems) with TaqMan gene expression assay probe / kit sets (Thermo Scientific). The primers used in this study were the following: GAPDH: Hs03929097_g1, SIRPy F:5'- AGGTGAGGAGGAGCTACAGA-3' (SEQ ID NO: 16), SIRPy R:5'GGTCCAACTCCTCTGAACCA-3' (SEQ ID NO: 17), SIRPy probe:5'CCCTGCTTCCCGTGGGACCCG-3' (SEQ ID NO: 18). SIRPy expressions between samples were normalized with respect to GAPDH. PCR amplification and target region analysis: Genomic DNA was isolated from control or SIRPy-classified T lymphocytes restimulated 9 days after CRISPR / Cas9 delivery using the Qiagen DNeasy Blood & Tissue Kit (Qiagen) according to the manufacturer's instructions. Genomic regions containing the SIRPy target site were amplified by PCR using the following primers: SIRPy F:5'CCAGATTGGGAAGGACAAGAGCTGT-3' (SEQ ID NO: 19), SIRPy R:5'GGCATGTTGTGAGGGTTAAATGAGA-3' (SEQ ID NO: 20). PCR products were analyzed by gel electrophoresis or purified on a 2% (w / v) agarose gel containing SYBR Safe (Life Technologies) using the Qiagen Gel Extraction Kit and subjected to Sanger sequencing. SIRPy expression in Treg lymphocytes and Treg suppression assay: To overexpress human SIRPy in human regulatory T lymphocytes, FACS-sorted CD4+CD25+CD127- Treg lymphocytes were activated with Dynabeads Human T-Activator CD3 / CD28 (ThermoFisher Scientific, No. 11131D) in a 1:1 ratio for 48 hours in the presence of 200 U / ml of human IL2 (202-IL-010 / CF, R&D). After 48 hours, the Dynabeads were removed, and the activated Treg lymphocytes were infected by centrifugation with retroviruses at 2000 rpm for 1 hour at 32°C. D5 post-infection by retrovirus centrifugation, human SIRPy GFP+ Treg lymphocytes were sorted by FACS and left to rest with human IL2 overnight before suppression assay preparation. To prepare the suppression assay, responsive CD4 T cells were isolated from stem cells of various healthy donors using the naive CD4 T cell isolation kit (130-094-131, Miltenyi), and isolated CD4 T cells were labeled using the cell trace violet proliferation kit (C34557, Thermo Fisher). Resting Treg cells were mixed with CTV-labeled responsive CD4 T cells in a different ratio. Allogeneic CD4+ cells were added to the reaction, and CD4 T cell proliferation was measured by CTV dilution. Mixed lymphocyte reaction and T lymphocyte proliferation assay. On day 6, after CRISPR-induced downregulation, T lymphocytes were subjected to mixed lymphocyte reactions (MLRs) or TCR-stimulated proliferation. MLRs were performed by incubating 100,000 pan-T cells from a healthy donor (responder) with 10,000 allogeneic dendritic cells (DCs). T lymphocyte proliferation was measured using a conventional thymidine 3H incorporation assay on day 7. For TCR stimulation, isolated T cells or CRISPR-suppressed T cells were plated on a labeled dilution of anti-CD3 Acm (OKT3, eBioscience) in a pre-coated 96-well round-bottom plate. Anti-CD47 Acm (B6H12), anti-SIRPy (LSB2.20), or control mouse IgG was added to the T cell cultures as directed. After 72 hours, T cell proliferation was measured using a conventional 3H-thymidine incorporation assay. SIRP-IgG fusion proteins: The extracellular domain of SIRPy and SIRPa was amplified by PCR and cloned into the pTT5.2-CMV vector in a frame containing a cDNA fragment encoding the Fe portion of human IgG fusion proteins. The chimeric SIRPy and SIRPa cDNAs were transiently expressed in cells 293 and the secreted SIRP-IgG fusion proteins were purified from the culture supernatant in protein A. Binding assay. SIRPy and SIRPa-FC IgG proteins (5 pg / ml) were incubated with various cells for 1 hour at 4°C in the absence of antibodies against SIRPy and CD47. The cells were then washed twice with FACS staining buffer and stained with anti-FC IgG antibody (PE) (1:50) for 15 minutes at 4°C. After two washes, the binding of the fusion proteins to the cells was detected by flow cytometry using a PE-conjugated human IgG anti-Fc antibody (No. 409304, Biolegend) followed by FACS analysis. In vitro antibody interference assay: Jurkat cells were incubated with SIRPy antibodies (10 pg / ml) for 30 minutes at room temperature. The cells were washed with FACS staining buffer and incubated with SIRPy-Fc fusion proteins (10 pg / ml) for 30 minutes at 4°C. The cells were then washed twice with FACS staining buffer and stained with anti-Fc IgG (PE) antibody (No. 409304, Biolegend, 1:50) for 15 minutes at 4°C. After two washes, the binding of the fusion proteins to the cells was detected by flow cytometry followed by FACS analysis. Antibody crosslinking and T-cell proliferation assay: 96-well plates were coated with 10 pg / ml of SIRPy antibodies (50 pl / well) overnight at 4°C. The following day, pan-T cells from healthy donors were seeded into the plate wells and the T cells were stimulated with the human CD3 / CD28 T-cell activator ImmunoCult™ (No. 10971, Stemcell Technologies). T-cell proliferation was measured using a conventional 3H thymidine incorporation assay on D3. The cell culture supernatant was collected and analyzed by cytometry bead assembly (CBA) (No. 558269, BD Biosciences). Statistical analysis: Statistical significance was determined by performing the t-test with Graphpad Prism. Significance is indicated as ***p < 0.0002, **p < 0.0021, *p < 0.0332 and ns p > 0.05. EXAMPLE 2 This example demonstrates that SIRPy is highly expressed in T lymphocytes. To study the function of SIRPy in T lymphocytes, the SIRPy expression profile in immune cell populations was first examined. Antibody specificity for SIRPy was confirmed by the specific recognition of the overexpressed SIRPy protein on the cell surface of 293T cells (Figure 1A). SIRPy staining on the cell surface of human CMSP cells showed that SIRPy is primarily expressed on CD4+ and CD8+ T lymphocytes, but not on CD14+ monocytes (Figure 1B). SIRPy showed high expression levels on resting-stage human CD4+ and CD8+ T lymphocytes. Natural killer (NKT) T lymphocytes also showed positive expression of SIRPy on their cell surface. These data are consistent with previous studies (Piccio et al., Blood, 105:2421-2427(2005)), which indicate that SIRPy expression is specific to T lymphocytes. Previous studies (Piccio et al., Blood, 105:2421-2427 (2005)) have shown that binding of the SIRPy receptor by the anti-SIRPy antibody acts as a costimulatory factor for T lymphocyte proliferation, suggesting a potential interaction between SIRPy and the T lymphocyte receptor (TCR). To test whether SIRPy expression is regulated by TCR signaling, T lymphocytes were stimulated with anti-CD3 and anti-CD28 antibodies, and the level of SIRPy expression by the stimulated T lymphocytes was examined. SIRPy maintained a high level of expression on the T lymphocytes, and its expression level was not altered during TCR stimulation (Figure 1C). iviA / a / zuz i / ui oyor EXAMPLE 3 This example demonstrates that SIRPy has increased its expression in memory T lymphocytes and in exhausted T lymphocytes infiltrated into the tumor. To better understand the SIRPy expression profile in subsets of effector and memory T cells, T cells from stem cells of multiple healthy donors were stained using antibodies. Undifferentiated T cells, core memory T cells, memory effectors, and effectors were identified by CD45RA and CCR7 staining. CD8+ memory T cells showed significantly increased SIRPy expression compared to effector and undifferentiated T cells (Figures 2A and 2B). Within the CD4+ T cell population, core memory CD4+ T cells showed higher SIRPy expression than effector T cells (Figures 2A and 2B). These data suggest that SIRPy may contribute to T cell memory function during immune regulation. Interestingly, single-cell RNA sequencing of tumor-infiltrating T lymphocytes showed that SIRPy is highly expressed in exhausted CD8+ T lymphocytes and tumor Tregs isolated from various human cancers, including HCC, CRC, and lung cancer (Figures 3A–3C). Because the association of SIRPy with tumor-infiltrating exhausted CD8+ T lymphocytes in tumors had not been previously reported, its expression and regulation in exhausted CD8+ T lymphocytes obtained in vitro were further characterized. SIRPy protein expression increased in CD8+ T lymphocytes that were repeatedly stimulated in vitro with a low dose of aCD3 TCR activation, a condition that limits T lymphocyte exhaustion (Figure 4).The increased expression pattern of SIRPy in exhausted T lymphocytes correlates with decreased production of effector cytokines and increased expression of other T lymphocyte exhaustion markers such as Tim3 and PD1, suggesting that SIRPy could serve as a marker for T lymphocyte exhaustion within the tumor microenvironment. EXAMPLE 4 This example demonstrates that SIRPy inhibits the release of effector cytokines from T lymphocytes. To study the function of SIRPy in T lymphocytes, retrovirus-mediated SIRPy overexpression was performed in T lymphocytes to mimic the high SIRPy expression in tumor-infiltrating CD8 T lymphocytes. Increased SIRPy expression was observed in CD8 T lymphocytes on day 3 post-retroviral infection (Figure 5B). Interestingly, CD8 T lymphocytes with overexpressed SIRPy produced significantly less IFN-γ than control virus-infected cells (Figure 5C–5D), supporting an inhibitory role for SIRPy in CD8 T lymphocytes. iviA / a / zuz i / ui oyor To further assess whether SIRPy is a negative regulator of T cell effector function, SIRPy expression levels in human T cells were downregulated using CRISPR. The success of CRISPR-induced SIRPy downregulation was evaluated at the genomic, mRNA, and protein levels. CRISPR delivery of guide RNAs (gRNAs) for SIRPy led to the deletion of the SIRPy genomic coding region that targeted SIRPy, significantly reducing SIRPy mRNA expression and SIRPy protein expression on the surface of T cells (Figure 6B–6E). In particular, reduced SIRPy expression significantly enhanced IFNγ secretion in CD8+ T cells when stimulated with TCR signaling in vitro (Figure 6F), indicating that SIRPy acts as a negative regulator of T cells.As noted in this document, these results were surprising given previous studies that suggested SIRPy as a costimulatory molecule of T lymphocytes (Piccio et al., Blood 105(6): 2421-2427 (2005); Leitner et al., Immunol Letters 128(2): 89-97 (2010)). EXAMPLE 5 This example demonstrates that SIRPy enhances the suppressive function of regulatory T lymphocytes and that monoclonal antibodies against SIRPy have an inhibitory effect on T lymphocyte proliferation. The RNA sequencing profile above in tumor-infiltrating T lymphocytes also suggests that SIRPy is upregulated in Tregs within HCC, CRC, and lung cancer (Figures 3A–3C). Additionally, increased SIRPy expression has been demonstrated in breast cancer (Reference: dataset GSE89225; Pitas et al. Immunity. November 15, 2016; 45(5):1122–1134). Higher SIRPy expression in tumor-infiltrating Tregs, compared to expression in non-Treg lymphocytes, was confirmed in NSCLC tumor samples (Figure 7A). Overexpression of SIRPy in human Tregs by retroviral transduction did not change FOXP3 expression levels in Tregs (Figures 7C–7D). However, SIRPy enhanced the suppressive activity of Tregs on T lymphocyte proliferation in the in vitro suppression assay (Figure 7E-7F).These data suggest that increased SIRPy expression in Tregs within the tumor environment contributes to the suppression of effector T cell function. These data also suggest that SIRPy inhibition may lead to enhanced levels of T cell proliferation within the tumor environment. Previous studies (Piccio et al., Blood, 105:2421-2427 (2005)) indicated that CD47 is a ligand for SIRPy. Piccio et al. also demonstrated that anti-SIRPy Acm and anti-CD47 Acm inhibited T cell proliferation and that SIRPy binding co-stimulated T cell proliferation, results that support SIRPy as a positive regulator of T cell function. However, using SIRPy overexpression and a SIRPy downregulation system, the studies described herein suggest that SIRPy is a negative regulator of T cell function. To further examine the discrepancy between the previous results and those described herein, the function of Acm against SIRPy during in vitro T cell proliferation was assayed.To examine functional blocking Acms that can block the interaction between SIRPy and CD47, SIRPy and CD47 were depleted in Jurkat T lymphocytes using CRISPR (Figure 8A). Using CD47-depleted cell lines, it was confirmed that SIRPy binds to the surface of T lymphocytes in a CD47-dependent manner (Figure 8B). Additionally, the Acm clones LSB2.20 and 0X119, which functionally block the SIRPy-CD47 interaction in Jurkat T lymphocytes, were identified through an in vitro binding assay (Figure 8C). During mixed lymphocyte reactions (MLRs), some anti-SIRPy antibodies inhibited T lymphocyte proliferation (Figure 8D). Furthermore, anti-SIRPy antibody treatment inhibited T lymphocyte activation in the presence of serial dilutions of a TCR ligand (8E). Interestingly, the inhibitory effect of the anti-SIRPy antibody was independent of the presence of SIRPy (Figure 8F), as the inhibitory effect was still observed when the SIRPG gene was deleted by the CRISPR-mediated method, as mentioned above. It is possible that the activities of these particular antibodies may be due to nonspecific effects or that the fragments in SIRPy that interact with CD47 are also required for interaction with other proteins to mediate their activity. EXAMPLE 6 This example demonstrates that anti-SIRPy monoclonal antibodies that bind to a particular SIRPy epitope can enhance T lymphocyte proliferation and function. To explore the inhibitory effect of SIRPy on T cell function, a panel of commercially available SIRPy antibodies was examined for their ability to bind to SIRPy and act as blockers of the CD47-SIRPy interaction. T cells were treated with either anti-SIRPy monoclonal antibodies (clone LSB2.20, clone OX117, clone OX119, LSC484765, clone 4F8C10 (MAB21425)) or polyclonal anti-SIRPy antibodies (AF4486), and antibody binding to T cells was assayed by FACS. As shown in Figure 9A, several anti-SIRPy antibodies were able to bind to endogenously expressed or exogenously overexpressed SIRPy on Jurkat cells (Figure 9A). The ability of anti-SIRPy antibodies to modify the binding interactions between SIRPy and its binding partners on T lymphocytes was evaluated by performing an in vitro antibody blocking assay. In this assay, SIRPy-Fc binds to T lymphocytes, possibly through its interaction with SIRPy binding partners, such as CD47 or other unidentified receptors, expressed by T lymphocytes. Currently, CD47 is the only known high-affinity receptor for SIRPy (Figure 8C). However, in the absence of any antibody to SIRPy, since SIRPy is also expressed on T lymphocytes, it can potentially interact with CD47 and / or other presumed c / s binding partners on the surface of T lymphocytes. As a result, these potential c / s interactions may inhibit SIRPy-Fc binding to its binding partners on T lymphocytes in this assay.However, if an anti-SIRPy antibody is pre-incubated, disrupting the cell-surface interaction between SIRPy and its binding partners, these binding partners could be released onto the cell surface to subsequently interact with the SIRPy-Fc protein in this assay. SIRPy-Fc binding to T lymphocytes was measured in the presence of various anti-SIRPy antibodies and compared to binding in the absence of anti-SIRPy antibodies. As shown in Figure 9B, the cells were pre-treated with the LSB2 clone.The anti-SIRPy antibody clones LSB2.20 and 0X119 did not exhibit enhanced SIRPy-Fc binding, suggesting that disrupting the SIRPy-CD47 interaction with these antibody clones does not result in the release of more CD47 or other binding partners for further interaction with the SIRPy-Fc fusion proteins, even though these antibodies have previously been shown to block the SIRPy-CD47 interaction. These data suggested that the affinity of these antibodies might not be strong enough to release the c / s interaction between T cell surfaces, or that CD47 and SIRPy do not interact c / s at the cell surface. Furthermore, these antibodies also do not block potential interactions between SIRPy and other presumed binding partners. Interestingly, unlike clones LSB2.20 and 0X119, treatment with clone 0X117 showed enhanced SIRPy-Fc fusion protein binding.Since 0X119 is known to bind to epitopes on SIRPy other than those that interact with CD47 (Figure 9E), these results suggest that 0X117 can block interactions between SIRPy and other putative binding proteins on the Jurkat cell surface. Following treatment with the 0X117 clone, Jurkat cells released the putative binding partners for binding by the SIRPy-Fc fusion protein (Figure 9B). Furthermore, the study tested the effect of anti-SIRPy antibodies on T cell proliferation and IFNγ secretion. In this assay, T cells were treated with anti-SIRPy monoclonal antibodies (clone LSB2.20, clone 0X117, clone 0X119, LS-C484765, clone 4F8C10 (MAB21425), anti-SIRPy polyclonal antibodies (AF4486), one of three nonspecific IgG controls, or no antibody control. The levels of T cell proliferation and IFNγ production were measured (Figures 9C and 9D). Interestingly, treatment of T cells with the SIRPy antibody clone 0X117 resulted in the highest levels of T cell proliferation and IFNγ secretion in vitro (Figures 9C-9D). The level of IFNy secreted by T lymphocytes treated with 0X117 was twice the level of IFNy secreted by lymphocytes treated with LSB2.20 and more than 6 times the level of IFNy secreted by lymphocytes treated with 0X119.As described, the fab fragment of the anti-SIRPy monoclonal antibody clone 0X117 binds to SIRPy at the interface of the first and second immunoglobulin domains (D1 and D2) of SIRPy (Nettleship et al., BMC Struct Biol 13: 13 (2013)), a region distinct from D1 (which interacts with CD47). Furthermore, the epitope to which 0X117 binds is distinct from the epitope to which the SIRPy monoclonal antibody clones 0X119 and LSB2 bind.20 This suggests that the T-cell proliferation and IFN-γ secretion observed with 0X117 are likely not caused by a direct blockade of CD47 binding to SIRPy. Figure 10 provides a summary of the results of previous assays conducted with the commercially available anti-SIRPy antibody panel. Taken together, these data do not support a specific costimulatory function of SIRPy, particularly through its interaction with CD47. Instead, the inventors identified a novel inhibitory function of SIRPy in T cell proliferation, activation, and cytokine production. Certain antibodies can interfere with this inhibitory function of SIRPy and enhance T cell activities, which could be achieved by blocking the interaction between CD47 and SIRPy. These data also suggest that the T cell inhibitory function of SIRPy may be mediated through epitopes unique to SIRPy and that molecules that bind to the D1 / D2 interface of SIRPy, similar to what is achieved by OX117 but without the limitation, may be useful for enhancing T cell function. EXAMPLE 7 This example demonstrates that SIRP inhibitors enhance an immune response against a tumor or cancer in a subject. T lymphocytes can destroy cancer cells when they recognize specific tumor antigens. To amplify the specific destructive effect of T lymphocytes, they are technically engineered to express tumor antigen-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs), thereby destroying cancer cells. CRISPR suppression of SIRPy is performed in antigen-specific TCR-T or CAR-T lymphocytes. Human cancer cells expressing the specific tumor antigen are co-cultured with control antigen-specific T lymphocytes or SIRPy-suppressed T lymphocytes in vitro to measure the antitumor immune response. The destructive activity of SIRPy-suppressed antigen-specific T lymphocytes is measured by quantifying the surviving cancer cells. Secreted IFN-γ is detected using a conventional ELISA assay.SIRPy-suppressed antigen-specific T lymphocytes exhibit increased IFNγ secretion and increased destruction of cancer cells. Tumor-specific antigens include, but are not limited to, NY-ESO-1 and MARTI / Melan-A. EXAMPLE 8 This example demonstrates that SIRP inhibitors lead to reduced tumor size and / or reduced tumor growth in a subject. SIRPy is not expressed in mouse cells. To establish a mouse tumor model for analyzing the effect of SIRPy on tumor growth, immunodeficient NOD scid gamma (NSG) mice are implanted with finely ground human cancer cells or patient-derived tumors expressing specific tumor antigens. SIRPy-suppressed or control antigen-specific T lymphocytes are engineered and expanded in vitro. After a tumor reaches a specified size (e.g., 50–120 mm³ in volume), SIRPy-suppressed or control antigen-specific T lymphocytes are adoptively transferred into NSG mice, and tumor size is measured. Specific tumor antigens include, but are not limited to, NY-ESO-1 and MART1 / MelanA. Mice transferred with SIRPy-suppressed antigen-specific T lymphocytes exhibit reduced tumor size and growth. To establish an in vivo tumor model to test the effect of SIRPγ inhibitors on the tumor immune response, humanized NSG mice (HuNSGs) are generated by transplantation of human pluripotent stem cells (HPSCs). Twelve weeks post-transplantation of human CD34+ HPSCs, human cancer cells are injected into mice to induce tumor development. Alternatively, for the patient-derived xenograft (PDX) tumor model, finely ground patient tumors are injected subcutaneously into HuNSG mice. Treatment is initiated when the tumors reach a certain size (e.g., 50–120 mm³ in volume). SIRPγ inhibitors are injected intravenously into HuNSG mice, and tumor size and volume are measured. Mice treated with SIRPy inhibitors exhibit reduced tumor size and growth. All references, including publications, patent applications and patents, cited herein are incorporated by reference to the same degree as if each reference were individually and specifically indicated as being incorporated by reference and set out in full herein. The use of the terms "a" and "an," and "the" and similar referents used in the context of the disclosure description (especially in the context of the following claims) should be construed as encompassing both the singular and the plural, unless otherwise stated herein or clearly contradicted by the context. The expressions comprising, having, including, and containing should be construed as open-ended expressions (i.e., as expressions meaning including, but not limited to), unless otherwise stated. The recitation of value intervals in this document is merely intended as a shorthand method for referring individually to each separate value that falls within the interval and each extreme value, unless otherwise stated herein, and each separate value and extreme value is incorporated into the descriptive memory as if recited individually in this document. All methods described herein may be performed in any suitable order unless otherwise stated herein or clearly contradicted by the context. The use of any and all examples or illustrative expressions (e.g., such as) provided herein is intended merely to further illuminate the disclosure and does not limit the scope of the disclosure unless otherwise claimed. Nothing in the specification should be construed as indicating that any unclaimed element is essential to the implementation of the disclosure. This document describes preferred embodiments of the disclosure herein, including the best manner known to the inventors for carrying out the disclosure. Variations from the preferred embodiments may be apparent to those skilled in the art upon reading the foregoing description. The inventors expect that those skilled in the art will employ such variations as appropriate, and the inventors do not intend for the disclosure to be put into practice in a manner different from that specifically described herein. Accordingly, this disclosure includes all modifications and equivalents of the subject matter recited in the appended claims to the extent permitted by applicable law.Furthermore, any combination of the elements described above in all possible variations thereof is included in the disclosure, unless otherwise stated herein, or unless the context clearly contradicts it.

Claims

1. A method of treating a subject with a tumor or cancer, comprising administering to the subject a SIRPy-binding molecule in an amount effective to treat the tumor or cancer in the subject.

2. A method of increasing effector activity or reducing suppressor activity of T lymphocytes in a subject with a tumor or cancer, comprising administering to the subject a SIRPy-binding molecule in an amount effective to increase effector activity or reduce suppressor activity in the subject.

3. A method of enhancing an immune response against a tumor or cancer in a subject, comprising administering to the subject a SIRPy-binding molecule in an amount effective to enhance an immune response against a tumor or cancer.

4. The method of claim 3, wherein the immune response is mediated by T lymphocytes.

5. The method of any one of claims 2-4, wherein the T lymphocytes are located within a tumor or tumor microenvironment.

6. The method of any one of claims 2-5, wherein the T lymphocytes are tumor-infiltrating T lymphocytes.

7. The method of claim 2-5, wherein the T lymphocytes are regulatory T lymphocytes (the Tregs).

8. The method of any one of claims 2-5, wherein the T lymphocytes are depleted T lymphocytes, optionally, depleted CD8+ T lymphocytes.

9. The method of any one of claims 2-5, wherein the T lymphocytes are memory lymphocytes.

10. The method of claim 9, wherein the memory lymphocytes are CD8+ memory lymphocytes or central CD4+ memory lymphocytes.

11. The method of any one of the preceding claims, wherein the SIRPy-binding molecule is a SIRPy inhibitor.

12. The method of claim 11, wherein the SIRPy inhibitor reduces the expression of SIRPy in the subject's cells, optionally wherein the SIRPy inhibitor reduces the expression of SIRPy on the cell surface in the subject's T lymphocytes.

13. The method of claim 12, wherein the T lymphocytes are effector T lymphocytes of the subject.

14. The method of any one of claims 11-13, wherein the SIRPy inhibitor reduces a binding interaction between SIRPy and a SIRPy binding partner.

15. The method of claim 14, wherein the SIRPy bonding partner is CD47.

16. The method of any one of the preceding claims, wherein the SIRPy-binding molecule binds to the immunoglobulin (Ig) domain 1 (D1) of SIRPy.

17. The method of any one of the preceding claims, wherein the SIRPy-binding molecule binds to the D1 and Ig domain 2 (D2) of SIRPy.

18. The method of any one of the preceding claims, wherein the SIRPy-binding molecule binds to both D1 and D2, optionally at the interface between D1 and D2.

19. The method of any one of the preceding claims, wherein the SIRPy-binding molecule binds to the epitope to which the SIRPy monoclonal antibody 0X117 binds.

20. The method of any one of the preceding claims, wherein the SIRPy-binding molecule competes with OX117 for SIRPy binding.

21. The method of claim 20 wherein the SIRPy-binding molecule binds to SIRPy with the same or greater affinity than 0X117.

22. The method of any one of the preceding claims, wherein the SIRPy binding molecule is an antigen-binding fragment thereof.

23. The method of any one of the preceding claims, wherein the SIRPy-binding molecule forms hydrogen bonds with one or more of the amino acid residues Q8, E10, G109, K11, L12 and D149 of SIRPy.

24. The method of any one of the preceding claims, wherein the SIRPy-binding molecule causes a conformational change of SIRPy after binding to SIRPy.

25. The method of any one of the preceding claims, wherein the SIRPy-binding molecule simultaneously binds to two SIRPy molecules or promotes SIRPy dimerization.

26. The method of any one of the preceding claims, wherein the SIRPy-binding molecule binds to an epitope that does not overlap with the CD47-binding site.

27. The method of any one of the preceding claims, wherein the SIRPy-binding molecule is an antigen-binding protein.

28. The method of claim 27, wherein the antigen-binding protein is an antibody, an antigen-binding antibody fragment, or an antibody protein product.

29. The method of claim 27 or 28, wherein the antigen-binding protein binds to an epitope within the CD47 binding site of SIRPy.

30. The method of any one of the preceding claims, wherein the subject has hepatocellular carcinoma (HCC), colorectal cancer (CRC), lung cancer, optionally, non-small cell lung cancer (NSCLC).

31. A method of treating a subject with a tumor or cancer, comprising enhancing an immune response against the tumor or cancer in the subject in accordance with any one of the preceding claims.

32. A method of treating a subject with a tumor or cancer, comprising increasing the effector activity or reducing the suppressive activity of T lymphocytes in the subject in accordance with any one of the preceding claims.