SIRP1 Antibody

What is the SIRPα/CD47 axis and why is it important in cancer research?

The SIRPα/CD47 axis functions as a critical innate immune checkpoint that enables cancer cell escape from macrophage phagocytosis. SIRPα is an Ig-like protein predominantly expressed on myeloid cells including macrophages, dendritic cells, and neutrophils, while CD47 (also known as integrin-associated protein) is widely expressed on normal and cancer cells . When CD47 on cancer cells binds to SIRPα on macrophages, it generates a "don't eat me" signal that inhibits phagocytosis, thereby facilitating immune evasion . This pathway has emerged as a significant target for cancer immunotherapy in both solid tumors and hematological malignancies .

The importance of this axis lies in its fundamental role in regulating myeloid cell-target cell signal transduction and its potential as a therapeutic target. By disrupting this interaction, researchers aim to enhance the immune system's ability to recognize and eliminate cancer cells.

How does SIRP1 antibody differ from other anti-SIRPα antibodies?

SIRP1 antibody is differentiated from other reported anti-SIRPα antibodies primarily by its ability to induce phagocytosis of both solid and hematologic tumor cell lines by human monocyte-derived macrophages as a single agent . While other anti-SIRPα antibodies typically require combination with tumor-opsonizing antibodies to effectively induce phagocytosis, SIRP1 demonstrates this capability independently .

The mechanism of SIRP1 is distinct: it directly blocks SIRPα/CD47 interaction and induces internalization of SIRPα/antibody complexes, which reduces macrophage SIRPα surface levels . In contrast, other anti-SIRPα antibodies like SIRP-2 act via disruption of higher-order SIRPα structures on macrophages . Both SIRP-1 and SIRP-2 engage FcγRII, which is required for their single-agent phagocytic activity .

Additionally, SIRP1 binds to both human SIRPα variants 1 and 2 (the most common variants in the human population), making it broadly applicable across genetically diverse populations .

What is the structural basis for SIRP1 antibody interactions with SIRPα?

SIRP1 antibody binds to the extracellular domain of SIRPα, which contains three Ig-like domains . The binding is primarily directed at the N-terminal domain of SIRPα, where most sequence differences between SIRPα variants exist . The interaction is characterized by high affinity binding to both common alleles of SIRPα (variants 1 and 2) .

Surface plasmon resonance (SPR) analysis has been used to characterize these interactions, determining binding kinetics and affinity constants . For example, in one study, SIRP analytes were injected in a "one-shot" kinetic mode and flowed over immobilized anti-SIRPα antibodies to determine KD values . Epitope binning was carried out using a classical sandwich approach to understand the precise binding regions .

The structural insights into these interactions provide the foundation for understanding how SIRP1 antibody disrupts the SIRPα/CD47 signaling pathway, ultimately leading to enhanced phagocytosis of cancer cells.

How are SIRP1 antibodies typically generated and characterized in laboratory settings?

Generation of SIRP1 antibodies typically follows these methodological steps:

• Immunization: Wild-type mice are immunized with recombinant human SIRPα containing all three extracellular immunoglobulin domains fused to GST .

• Hybridoma production: Following repetitive immunization, spleen cells are fused with nonsecreting myeloma cells (such as P3 × 63Ag8.653) to create hybridomas .

• Screening: Clones are screened for reactivity to human SIRPαV1 .

• Sequencing and characterization: RNA is isolated from successful hybridoma cells, and immunoglobulin cDNA is synthesized using established methods with deoxythymidine oligonucleotide primers and reverse transcriptase .

• Expression and purification: Mouse clones of SIRP-1 on a murine IgG1 backbone are expressed (for instance, by expression services like Evitria) and purified using affinity chromatography methods such as MabSelect SuRe resin .

Characterization typically involves:

• Binding assays using surface plasmon resonance (SPR) to determine affinity constants

• Cell binding assays on primary human, monkey, and mouse monocytes using fluorescently labeled antibodies

• Functional assessment through phagocytosis assays using both SIRPα homozygous and heterozygous v1 and v2 macrophages

• Cross-reactivity testing across species (human, mouse, cynomolgus monkey)

What are the key methodologies for assessing SIRP1 antibody efficacy in preclinical models?

Assessment of SIRP1 antibody efficacy in preclinical models involves several key methodologies:

• In vitro phagocytosis assays: These assays evaluate the ability of SIRP1 antibody to induce phagocytosis of cancer cells by human monocyte-derived macrophages. This involves co-culturing macrophages with fluorescently labeled tumor cells in the presence of SIRP1 antibodies and quantifying phagocytosis through flow cytometry or microscopy .

• Mechanism of action studies:

  • SIRPα/CD47 binding disruption: Assessed through competitive binding assays

  • SIRPα internalization: Measured by flow cytometry to quantify surface SIRPα levels after antibody treatment

  • FcγR engagement: Evaluated using Fc receptor blocking antibodies or macrophages from FcγR knockout models

• Tumor xenograft models: Human cell line-derived or patient-derived tumors are implanted into immunodeficient mice (such as MITRG or MISTRG mice) humanized with human immune cells. These models allow for the evaluation of TAM (tumor-associated macrophage) status and anti-tumor therapy targeting TAMs in vivo .

• Syngeneic tumor models: Used to evaluate the combination of anti-SIRPα antibodies with other immunomodulatory agents, such as anti-PD-1 antibodies. For example, the MC38 colon cancer model has been used to assess how anti-SIRPα antibodies potentiate the efficacy of anti-tumor and anti-PD-1 antibodies .

• Pharmacokinetic and pharmacodynamic studies: These studies assess antibody distribution, target occupancy, and safety in non-human primates (such as cynomolgus monkeys) .

How can researchers effectively evaluate SIRPα variant specificity when developing SIRP1 antibodies?

Evaluating SIRPα variant specificity requires a methodical approach:

• Recombinant protein binding assays: Researchers should express the different SIRPα variants (primarily variants 1 and 2) as recombinant proteins and test binding of SIRP1 antibody candidates using ELISA or surface plasmon resonance (SPR). This quantifies binding affinities across variants .

• Cell-based binding assays: Researchers can utilize cells expressing different SIRPα variants and assess antibody binding through flow cytometry. For human variants, primary monocytes isolated from donors with known SIRPα genotypes can be used .

• Phagocytosis assays with variant-specific macrophages: Macrophages derived from donors homozygous or heterozygous for SIRPα variants 1 and 2 should be tested in phagocytosis assays to ensure the antibody functions across genetic variants . This is crucial since SIRPα is polymorphic with two common alleles that differ markedly in sequence (13 differences in their N-terminal domains) .

• Epitope mapping: Techniques such as hydrogen-deuterium exchange mass spectrometry, X-ray crystallography, or epitope binning using SPR can identify the specific binding regions. This helps determine if the antibody targets conserved or variable regions across SIRPα variants .

• Cross-species reactivity: Testing binding to SIRPα from different species (human, mouse, cynomolgus monkey) provides additional information about epitope conservation and can facilitate preclinical development .

This comprehensive evaluation ensures that developed SIRP1 antibodies will maintain efficacy across the genetic diversity of the human population.

How do SIRP1 antibodies compare with anti-CD47 antibodies in clinical development?

SIRP1 antibodies and anti-CD47 antibodies differ in several key aspects that impact their clinical development:

• Target expression profile:

  • SIRP1 antibodies target SIRPα, which has restricted expression primarily on myeloid cells (macrophages, dendritic cells, and neutrophils) .

  • Anti-CD47 antibodies target CD47, which is ubiquitously expressed on normal cells, including red blood cells and platelets .

• Safety profile:

  • SIRP1 antibodies generally demonstrate fewer on-target, off-tumor effects due to the restricted expression of SIRPα .

  • Anti-CD47 antibodies frequently cause anemia and thrombocytopenia due to CD47 expression on erythrocytes and platelets, resulting in the antigen sink phenomenon .

• Mechanism of action:

  • SIRP1 antibodies like SIRP-1 directly block SIRPα/CD47 interaction and induce internalization of SIRPα/Ab complexes .

  • Anti-CD47 antibodies primarily block the interaction between CD47 on tumor cells and SIRPα on phagocytes .

• Clinical development status:

  • Anti-CD47 agents such as magrolimab and ALX-148 have progressed further in clinical development but have faced recent setbacks in Phase 3 trials .

  • Anti-SIRPα antibodies like CC-95251 and BI 765063 are in earlier clinical development stages, with BI 765063 showing clinical benefit as monotherapy in an ongoing phase 1 trial for solid malignancies .

• Efficacy in combination therapy:

  • Both SIRP1 antibodies and anti-CD47 antibodies enhance efficacy when combined with tumor-opsonizing antibodies like rituximab or obinutuzumab .

  • SIRP1 antibodies may have an advantage in their ability to induce single-agent phagocytosis .

What are the current challenges in translating SIRP1 antibody research to clinical applications?

Several challenges exist in translating SIRP1 antibody research to clinical applications:

• SIRPα polymorphism: SIRPα is highly polymorphic with multiple variants in the human population. Ensuring that SIRP1 antibodies bind effectively to all common variants (particularly variants 1 and 2) is essential for broad clinical applicability .

• Optimal dosing and scheduling: Determining the optimal dose and schedule to achieve consistent SIRPα occupancy on myeloid cells while minimizing potential adverse effects remains challenging .

• Patient selection biomarkers: Identifying biomarkers that predict which patients will respond best to SIRP1 antibody therapy is crucial. This might include assessing tumor microenvironment composition, particularly the presence and phenotype of tumor-associated macrophages .

• Combination strategies: While SIRP1 antibodies show single-agent activity in vitro, determining the optimal combinations with other agents (such as tumor-targeting antibodies, checkpoint inhibitors, or conventional therapies) for different cancer types is complex .

• Addressing resistance mechanisms: Understanding potential resistance mechanisms to SIRP1 antibody therapy, such as upregulation of alternative "don't eat me" signals (e.g., PD-L1/PD-1, CD24/Siglec-10), is necessary for developing effective long-term treatment strategies .

• Immunogenicity concerns: As with any antibody therapy, the potential for anti-drug antibodies that could neutralize SIRP1 antibodies must be addressed, particularly with repeated dosing .

• Addressing potential off-target effects: Since SIRP1 antibodies may bind to SIRPγ with varying affinity, potential effects on T cell function must be carefully monitored, although current data suggest no adverse effects on T cell proliferation .

How can SIRP1 antibodies be used to reprogram tumor-associated macrophages in cancer immunotherapy?

SIRP1 antibodies can reprogram tumor-associated macrophages (TAMs) from a protumoral (M2-like) to an antitumoral (M1-like) state through several mechanisms:

• Disruption of the "don't eat me" signal: By blocking the SIRPα/CD47 interaction, SIRP1 antibodies remove the inhibitory signal that prevents macrophages from phagocytosing cancer cells . This directly enhances the phagocytic activity of TAMs against tumor cells.

• FcγR engagement: SIRP1 antibodies engage FcγRII on macrophages, which is required for their single-agent phagocytic activity . This activation of Fc receptors can trigger pro-inflammatory signaling pathways that contribute to macrophage reprogramming.

• Modulation of TAM phenotype: Research in HIS-MITRG mice with human cell line-derived or patient-derived B cell lymphoma xenografts has demonstrated that anti-SIRPα antibodies combined with rituximab initiate the reprogramming of TAMs from a protumoral toward an antitumoral state .

• Enhancement of cytokine production: Anti-SIRPα antibodies can increase the production of pro-inflammatory cytokines by TAMs. In combination with anti-PD-1 therapy, they have been shown to induce dendritic cell activation and increase M1 TAMs, thus bridging innate and adaptive immunity .

• Reduction of SIRPα surface levels: SIRP1 antibody specifically induces internalization of SIRPα/antibody complexes, reducing macrophage SIRPα surface levels . This reduction in SIRPα availability may further contribute to shifting the balance toward an activated macrophage phenotype.

• Reversal of SHP1-dependent ADP repression: SIRPα signals through the phosphatase SHP1, which negatively regulates phagocytosis. Studies have shown that SHP1 acts as a downstream effector of SIRPα and is an upstream negative regulator of SYK-mediated antibody-dependent phagocytosis (ADP) . By disrupting SIRPα signaling, SIRP1 antibodies can reverse this SHP1-dependent repression of phagocytosis.

• Restoration of chemokine secretion: Selective SIRPα blockade stimulates T-cell recruitment into tumors by restoring macrophage chemokine secretion and promoting tumor-antigen cross-presentation .

What are the mechanisms by which SIRP1 antibodies might overcome resistance to existing cancer immunotherapies?

SIRP1 antibodies could overcome resistance to existing cancer immunotherapies through several mechanisms:

• Targeting different immune cell populations: While many current immunotherapies focus on T cells (e.g., PD-1/PD-L1 inhibitors), SIRP1 antibodies primarily act on myeloid cells, including macrophages and dendritic cells . This provides a complementary approach that could overcome resistance mediated by T cell dysfunction or exclusion.

• Enhancing antigen presentation: By activating macrophages and dendritic cells, SIRP1 antibodies can enhance phagocytosis of tumor cells and subsequent antigen presentation to T cells. This can help initiate or reinvigorate T cell responses in tumors that have developed resistance to direct T cell-targeting approaches .

• Converting immunosuppressive macrophages: Many tumors are infiltrated with immunosuppressive M2-like macrophages that contribute to therapy resistance. SIRP1 antibodies can help reprogram these macrophages toward a more anti-tumoral M1-like phenotype, reversing their immunosuppressive effects .

• Synergizing with tumor-opsonizing antibodies: SIRP1 antibodies enhance the efficacy of tumor-targeting antibodies like rituximab by enhancing antibody-dependent cellular phagocytosis (ADCP) . This can overcome resistance to these antibodies that occurs when macrophage phagocytic activity is suppressed by SIRPα signaling.

• Disrupting SHP1-dependent resistance pathways: SHP1 is a downstream effector of SIRPα and an upstream negative regulator of SYK-mediated antibody-dependent phagocytosis. By disrupting SIRPα signaling, SIRP1 antibodies can reverse SHP1-dependent suppression of phagocytosis, potentially overcoming resistance mechanisms involving this pathway .

• Modulating cytokine production: SIRP1 antibodies can alter the cytokine profile within the tumor microenvironment by activating myeloid cells, potentially converting an immunosuppressive environment to one that supports anti-tumor immunity .

How might humanized SIRP1 antibodies be optimized for improved efficacy and reduced immunogenicity?

Optimization of humanized SIRP1 antibodies for improved efficacy and reduced immunogenicity involves several strategies:

• Optimal humanization techniques:

  • Careful grafting of chicken variable regions onto human framework regions (e.g., human lambda light chain IGVL3 frameworks)

  • CDR (complementarity-determining region) grafting with minimal framework changes to preserve binding properties

  • Use of structural information to guide humanization decisions

• Engineering optimal Fc domains:

  • Selection of appropriate IgG isotypes based on desired effector functions

  • Fc engineering to enhance binding to specific FcγRs (particularly FcγRII, which is required for SIRP1 antibody function)

  • Potential glycoengineering to modify effector functions and half-life

• Affinity optimization:

  • Fine-tuning binding affinity to both SIRPα alleles (v1 and v2) to ensure broad population coverage

  • Optimization of binding kinetics (kon and koff rates) to achieve desired pharmacodynamic effects

• Reducing SIRPγ cross-reactivity:

  • Engineering antibodies to minimize binding to SIRPγ while maintaining high affinity for SIRPα variants

  • Careful epitope selection to target regions that differ between SIRPα and SIRPγ

• Formulation optimization:

  • Development of stable formulations to minimize aggregation, which can increase immunogenicity

  • Exploration of alternative delivery methods or formulations to maximize tumor penetration

• T-cell epitope analysis and deimmunization:

  • In silico and in vitro assessment of potential T-cell epitopes that could drive anti-drug antibody responses

  • Strategic mutations to remove immunogenic epitopes without affecting binding properties

• Development of functional assays:

  • Creation of comprehensive panel of assays to evaluate binding to SIRPα variants, FcγR engagement, and phagocytosis induction

  • Use of humanized mouse models for in vivo efficacy and immunogenicity assessment

What novel combinatorial approaches with SIRP1 antibodies might yield synergistic anti-tumor effects?

Several novel combinatorial approaches with SIRP1 antibodies show promise for synergistic anti-tumor effects:

• Combination with other immune checkpoint inhibitors:

  • Anti-PD-1/PD-L1 antibodies: SIRP1 antibodies combined with anti-PD-1 have shown enhanced efficacy in syngeneic models, with increased DC activation, M1 TAMs, and T-cell effector function

  • Anti-CTLA-4 antibodies: Dual blockade of innate (SIRPα/CD47) and adaptive (CTLA-4) immune checkpoints could provide comprehensive immune activation

• Combination with tumor-targeting antibodies:

  • Classical tumor-targeting antibodies (rituximab, obinutuzumab, cetuximab): SIRP1 antibodies enhance antibody-dependent cellular phagocytosis induced by these agents

  • Anti-CD47 antibodies with different mechanisms: Combining SIRP1 with antibodies like AO-176 has shown enhanced phagocytosis in vitro

• Trispecific approaches:

  • Development of trispecific antibodies targeting SIRPα, tumor antigens, and activating FcγRs simultaneously

  • Combination of SIRP1 antibodies with bispecific T-cell engagers to leverage both innate and adaptive immunity

• Combination with epigenetic modifiers:

  • HDAC inhibitors: These have been shown to modulate macrophage phenotype and could complement SIRP1 antibody effects

  • DNA methyltransferase inhibitors (DNMTi): Azacitidine and other DNMTi agents could synergize with SIRP1 antibodies by altering immune gene expression

• Combination with targeted therapies:

  • Small molecule inhibitors targeting oncogenic pathways (BRAF, MEK, BTK inhibitors)

  • Tyrosine kinase inhibitors (TKIs) that may also modulate immune cell function

• Combination with conventional therapies:

  • Radiation therapy: Can induce immunogenic cell death and release tumor antigens

  • Chemotherapy agents: Certain chemotherapies can deplete immunosuppressive cells or induce immunogenic cell death

• Novel immune-stimulating approaches:

  • TLR agonists: Could enhance myeloid cell activation in combination with SIRP1 antibodies

  • CD40 agonists: Activation of CD40 on dendritic cells and macrophages could complement SIRPα blockade

• Metabolic modulators:

  • IDO inhibitors: Could reverse metabolic immunosuppression in the tumor microenvironment

  • Glutaminase inhibitors: May alter macrophage metabolism and enhance anti-tumor effects

Research has shown that combining anti-SIRPα agents with tumor-opsonizing antibodies and other immune checkpoint inhibitors can create a multi-pronged approach that targets both innate and adaptive immunity, potentially overcoming resistance mechanisms associated with single-agent therapies .

How can emerging technologies advance our understanding of SIRP1 antibody mechanisms and improve their development?

Emerging technologies are poised to significantly advance our understanding of SIRP1 antibody mechanisms and improve their development:

• Single-cell technologies:

  • Single-cell RNA sequencing can profile the transcriptional changes in individual macrophages and other immune cells following SIRP1 antibody treatment

  • Single-cell proteomics can identify changes in protein expression and phosphorylation status

  • These approaches can reveal heterogeneity in myeloid cell responses and identify specific cellular subsets that are most responsive to SIRP1 antibodies

• Advanced imaging techniques:

  • Intravital microscopy to visualize SIRP1 antibody-mediated phagocytosis in real-time in vivo

  • Multiplexed immunofluorescence to simultaneously track multiple cell types and markers in the tumor microenvironment

  • Super-resolution microscopy to visualize the molecular organization of SIRPα on the macrophage surface and how SIRP1 antibodies disrupt this organization

• CRISPR-Cas9 gene editing:

  • Systematic investigation of the role of different signaling molecules downstream of SIRPα

  • Generation of SIRPα variant-specific cell lines for antibody testing

  • Creation of humanized SIRPα knock-in mouse models for improved preclinical testing

• Artificial intelligence and machine learning:

  • Prediction of optimal antibody structures for targeting specific SIRPα epitopes

  • Analysis of complex datasets to identify biomarkers of response to SIRP1 antibody therapy

  • Design of optimal combination therapies based on multi-omics data

• Organoid and 3D culture systems:

  • Development of complex 3D culture systems incorporating tumor cells, macrophages, and other immune cells

  • Patient-derived organoids with autologous immune cells to test SIRP1 antibody efficacy in personalized models

• Improved humanized mouse models:

  • Further refinement of models like HIS-MITRG and MISTRG mice that express human cytokines and SIRPα

  • Development of models with more complete human immune system reconstitution for better assessment of both innate and adaptive immune responses to SIRP1 antibodies

• Antibody engineering platforms:

  • High-throughput antibody generation and screening approaches

  • Novel scaffolds beyond traditional antibodies, such as nanobodies or alternative binding proteins

  • Site-specific conjugation methods for creating precisely defined antibody-drug conjugates

These technologies can collectively provide deeper insights into the mechanisms of action of SIRP1 antibodies, facilitate the development of improved variants with enhanced efficacy and safety profiles, and enable more precise patient selection for clinical trials.

What key factors should researchers consider when selecting or developing SIRP1 antibodies for their specific research questions?

When selecting or developing SIRP1 antibodies for specific research questions, researchers should consider these key factors:

• Binding specificity and affinity:

  • Ensure the antibody binds to relevant SIRPα variants (v1 and v2) with appropriate affinity

  • Consider cross-reactivity with SIRPγ and potential effects on T cells

  • Evaluate species cross-reactivity (human, mouse, cynomolgus monkey) based on intended studies

• Functional mechanism:

  • Determine whether the research question requires an antibody that directly blocks CD47/SIRPα interaction (like SIRP-1) or disrupts higher-order SIRPα structures (like SIRP-2)

  • Consider whether SIRPα internalization is desirable for the specific application

• Fc functionality:

  • Select appropriate isotype based on whether FcγR engagement is necessary for the research question

  • Consider whether complement activation is desired or should be avoided

  • For in vivo studies, ensure compatibility with host FcγRs

• Clonality and format:

  • Decide between monoclonal, polyclonal, or recombinant antibodies based on application

  • Consider formats such as full-length antibodies, Fab fragments, or novel scaffolds

  • For imaging or specialized applications, evaluate conjugated versions (fluorescent dyes, enzymes)

• Validation status:

  • Assess the extent of validation for specific applications (flow cytometry, IHC, Western blot, functional assays)

  • Look for evidence of validation in relevant cell types and experimental systems

  • Consider reproducibility across different lots and sources

• Compatibility with experimental systems:

  • For in vitro studies, ensure compatibility with culture conditions

  • For in vivo studies, consider host species, potential immunogenicity, and dosing requirements

  • For translational research, evaluate clinical relevance and translatability

• Technical considerations:

  • Storage requirements and stability

  • Availability of matched isotype controls

  • Compatibility with other reagents in multiplex assays

Understanding these factors will help researchers select or develop SIRP1 antibodies that are optimally suited for their specific research questions, whether focused on basic mechanistic studies, preclinical therapeutic development, or clinical translation.

What are the most promising future directions for SIRP1 antibody research in cancer immunotherapy?

The most promising future directions for SIRP1 antibody research in cancer immunotherapy include:

• Developing next-generation anti-SIRPα agents:

  • Bispecific antibodies targeting both SIRPα and tumor antigens or immune activating receptors

  • Antibody-drug conjugates that deliver cytotoxic payloads specifically to SIRPα-expressing myeloid cells in the tumor microenvironment

  • Small molecule inhibitors targeting SIRPα signaling pathways as alternatives to antibodies

• Expanding beyond oncology:

  • Investigating SIRP1 antibodies in inflammatory and autoimmune diseases where myeloid cell dysfunction plays a role

  • Exploring applications in neurological disorders, considering the expression of SIRPα in the nervous system

  • Potential use in transplantation to modulate macrophage-mediated rejection

• Biomarker development:

  • Identifying predictive biomarkers of response to SIRP1 antibody therapy

  • Developing companion diagnostics for SIRPα variant typing

  • Establishing pharmacodynamic markers to optimize dosing regimens

• Novel combination strategies:

  • Rational combinations based on mechanistic understanding of tumor-immune interactions

  • Sequential or alternating therapy approaches to maximize immune activation while minimizing resistance

  • Intratumoral administration strategies to enhance local effects while reducing systemic toxicity

• Understanding resistance mechanisms:

  • Investigating how tumors might adapt to SIRP1 antibody therapy

  • Identifying alternative "don't eat me" signals that emerge during treatment

  • Developing strategies to overcome or prevent resistance

• Improving delivery and targeting:

  • Nanoparticle formulations to enhance tumor delivery

  • Tissue-specific targeting strategies to focus effects on tumor-associated macrophages

  • Long-acting formulations to reduce dosing frequency

• Translational platform development:

  • Creating improved humanized mouse models that better recapitulate human myeloid cell biology

  • Developing ex vivo human tumor slice culture systems with intact myeloid compartments

  • Establishing real-time imaging methods to visualize SIRP1 antibody effects in patients