CD45: The Immune Cell

1. CD45 Overview

CD45 (also known as PTPRC, Leukocyte Common Antigen) is a highly conserved transmembrane glycoprotein tyrosine phosphatase, widely expressed on the surface of all nucleated hematopoietic cells except mature red blood cells. It is a key regulatory factor for T-cell and B-cell antigen receptor signal transduction ^[1]. By regulating the phosphorylation status of Src family kinases (such as Lck and Fyn), CD45 determines the activation threshold of immune cells, influencing the strength and specificity of immune responses ^[2]. Dysfunction of CD45 is closely associated with various diseases, including immunodeficiencies, autoimmune diseases, leukemias, lymphomas, and several solid tumors. Furthermore, CD45 plays significant roles in innate immunity, inflammatory responses, and the regulation of the tumor microenvironment ^[1]. In recent years, CD45 splice variants, their signaling regulatory mechanisms, and their potential as therapeutic targets have become research hotspots ^[3].

2. Structure and Function of CD45

CD45 is encoded by 35 exons and has multiple splice variants (e.g., CD45RA, RB, RO, etc.), with different isoforms expressed specifically during immune cell differentiation and activation states ^[4]. Its extracellular domain is large in size, while the intracellular portion contains two phosphatase domains: D1, which possesses catalytic activity, and D2, whose function is not yet fully understood ^[1][4].

Fig. 1: Structure of CD45 (Source: PDB)

CD45 bidirectionally regulates the activation threshold of the TCR/BCR signaling pathways by dephosphorylating Src family kinases (e.g., Lck, Fyn), thereby influencing the intensity and specificity of immune cell responses ^[2]. It plays important roles in various immune cells including T cells, B cells, myeloid cells, and dendritic cells ^[5]. The spatial distribution and molecular exclusion of CD45 (e.g., its exclusion from the immunological synapse) are crucial for signal initiation ^[6].

3. CD45-Associated Signaling Pathways

CD45 influences immune cell function and disease progression by regulating multiple signaling pathways, primarily including:

TCR/BCR Signaling Pathways: CD45 regulates the phosphorylation of Lck/Fyn, affecting the TCR/BCR activation threshold ^[2]. In T cells, CD45 promotes T-cell receptor (TCR) signal transduction by dephosphorylating Lck, thereby regulating T cell activation and proliferation. In B cells, CD45 influences B cell development and function by modulating the B cell receptor (BCR) signaling pathway ^[7].
STAT3/PKC/ERK Pathways: In myeloid cells, tumor-associated macrophages, myeloma, etc., CD45 affects cell differentiation and proliferation by regulating signals such as STAT3, PKC, and ERK. For instance, in myeloma, the interaction of different CD45 isoforms with STAT3, PKC, and ERK regulates the proliferation of leukemia cells ^[8].
Wnt/β-catenin Pathway: In colorectal cancer, CD45 promotes Wnt signaling activity, enhancing tumor stemness and drug resistance. By regulating the Wnt signaling pathway, CD45 affects tumor cell proliferation and differentiation, thus playing a significant role in tumorigenesis and development ^[9].
TLR4 Pathway: The cytoplasmic tail fragment of CD45 can regulate immune responses in dendritic cells and T cells via TLR4 ^[5]. For example, in dendritic cells, the cytoplasmic tail fragment of CD45 modulates cell activation and function through the TLR4 signaling pathway.

4. CD45-Associated Diseases

4.1 Immunodeficiency and Autoimmune Diseases

CD45 plays a key role in maintaining immune system balance, and its dysfunction is closely linked to various immunodeficiencies and autoimmune diseases ^[2]. In severe combined immunodeficiency (SCID), abnormal CD45 expression can lead to blocked development of T and B cells, resulting in severe impairment of immune system function. Additionally, CD45 is involved in regulating the intensity and specificity of immune responses; its functional abnormalities in autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis (MS) may promote attacks on self-tissues ^[4]. Studies show that altered expression and function of CD45 in SLE patients are closely related to disease onset and progression. In MS, CD45 likely influences central nervous system inflammation by regulating T cell activation and migration. Modulating CD45 activity holds promise for providing new strategies to treat these diseases, potentially alleviating symptoms and improving patients' quality of life ^[10].

4.2 Tumors and Hematological Diseases

CD45 is closely associated with the occurrence, development, and treatment of various tumors and hematological diseases ^[1]. In leukemias, such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), abnormal CD45 expression may affect the proliferation, differentiation, and survival of leukemia cells. By regulating signaling pathways like the Wnt pathway, it may promote leukemia cell stemness and drug resistance, thereby influencing disease progression. In lymphomas, including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), CD45 may affect tumor cell immune escape and proliferation by modulating signal transduction in T and B cells. Furthermore, in myeloma, CD45 plays a significant role in the tumor microenvironment by regulating signaling pathways like STAT3, PKC, and ERK, impacting plasma cell development and function. These findings indicate that CD45 is not only crucial in the biological behavior of tumor cells but also represents a potential therapeutic target, providing a basis for developing new treatment strategies.

4.3 Inflammation and Cardiovascular Diseases

CD45 plays an important regulatory role in inflammatory responses and cardiovascular diseases ^[12]. In atherosclerosis, CD45 influences the development of inflammation and the formation of atherosclerotic plaques by regulating signaling pathways in B cells and endothelial cells. Additionally, in post-myocardial infarction valvular fibrosis, CD45 may participate in regulating the activation of B cells and endothelial cells, thereby affecting vascular inflammation and the fibrotic process. Research suggests that altered expression and function of CD45 in patients with atherosclerosis and post-myocardial infarction valvular fibrosis may be closely related to the pathogenesis of these diseases. Modulating CD45 activity could help alleviate inflammatory responses, improve symptoms of cardiovascular diseases, and offer new directions for their treatment.

4.4 Infection and Viral Immune Evasion

CD45 plays a vital role in the body's defense against viral infections; however, some viruses exploit CD45 to achieve immune evasion ^[13]. For example, adenovirus binds to CD45, forcing its dimerization, thereby inhibiting T cell receptor signaling, impeding T cell activation, and facilitating immune evasion. Cytomegalovirus also inhibits T cell signaling by modulating CD45 activity, avoiding recognition and clearance by the immune system. These viral evasion mechanisms weaken the host's immune response, allowing viral infections to persist. Studies indicate that modulating CD45 activity to enhance the immune response against viruses holds promise for providing new approaches in antiviral therapy, potentially leading to more effective viral clearance and protection against infection.

5. Latest Research Progress on CD45-Targeting Drugs

In recent years, significant progress has been made in the development of CD45-targeting drugs, moving from basic research towards diverse clinical applications. Anti-CD45 antibody-drug conjugates (ADCs) are being used for the precise elimination of hematological tumors and in conditioning regimens prior to hematopoietic stem cell transplantation; anti-CD45 radioantibodies have shown promising efficacy and safety in early clinical trials for various myeloid leukemias; additionally, strategies involving CD45 gene-edited CAR-T cells and immune reconstitution are emerging. CD45 is becoming an important target bridging immunoregulation and precision therapy, with its drug development progressively advancing from experimental validation towards clinical translation.

Drug	Mechanism of Action	Drug Type	Indications Under Investigation	R&D Institutions	Highest Phase
I-131-Apamistamab	CD45 Inhibitor	Antibody-Conjugated Radionuclide \| Therapeutic Radiopharmaceutical	Refractory Acute Myeloid Leukemia \| Relapsed Acute Myeloid Leukemia, etc.	Actinium Pharmaceuticals, Inc. \| The University of Texas Southwestern Medical Center	Phase 3
At 211 MAb BC8-B10	CD45 Inhibitor	Antibody-Conjugated Radionuclide \| Therapeutic Radiopharmaceutical	Tumor \| Relapsed Acute Lymphoblastic Leukemia \| Refractory Anemia with Excess Blasts, etc.	Fred Hutchinson Cancer Research Center \| Fred Hutchinson Cancer Center	Phase 2
ABO-21009	CD45 Inhibitor	Monoclonal Antibody	Rheumatoid Arthritis	AbolerIS Pharma	Phase 1
Anti-CD45-IGN ADC (Vor Biopharma)	CD45 Modulator	ADC	Hematopoietic Stem Cell Transplantation	Vor Biopharma, Inc.	Preclinical
MGTA-45	CD45 Inhibitor \| RNA Polymerase II Inhibitor	ADC	Leukemia	Magenta Therapeutics, Inc.	Preclinical
Anti-CD45 CAR-T cell therapy (Cimeio Therapeutics)	CD45 Modulator	CAR-T	Bone Marrow Tumors	Cimeio Therapeutics AG	Preclinical
VY-UC	CD45 Agonist	Cell Therapy	Multiple Myeloma	Vycellix, Inc.	Preclinical
CIM053-SG3376	CD45 Inhibitor	ADC	Tumor	Cimeio Therapeutics AG \| Universitätsspital Basel	Preclinical
TSC-102	CD45 Modulator \| Immunocytotoxicity \| T-cell Replacement	TCR-T Cell Therapy	Acute Lymphoblastic Leukemia \| Acute Myeloid Leukemia \| MyelodysplasticSyndromes	TScan Therapeutics, Inc.	Preclinical
TNX-4200	CD45 Agonist	Small Molecule Drug	Viral Infection	Tonix Pharmaceuticals Holding Corp.	Preclinical
Anti-CD45 CAR T-cell therapy (Perelman School of Medicine)	CD45 Modulator	CAR-T	Hematological Tumors	Perelman School of Medicine at the University of Pennsylvania	Preclinical
MGTA-ATACs (Heidelberg Pharma Research GmbH)	CD45 Modulator \| c-Kit Inhibitor	ADC	Genetic Diseases \| Hematological Tumors	Magenta Therapeutics, Inc. \| Heidelberg Pharma Research GmbH	Preclinical
CD45-targeted ETB (Molecular Templates)	CD45 Modulator	ADC	Tumor	Molecular Templates, Inc.	Preclinical
CIM-053	CD45 Modulator	ADC	Hematological Tumors	Cimeio Therapeutics AG	Preclinical
Anti-CD45 ADCs (ADC Therapeutics)	CD45 Modulator \| DNA Inhibitor	ADC	Adult Acute Myeloid Leukemia	ADC Therapeutics SA	Preclinical
Anti-CD45 antibody-drug conjugate (Magenta Therapeutics)	CD45 Inhibitor	ADC	Acute Myeloid Leukemia \| Atherosclerosis \| Autoimmune Diseases \| Bone Marrow Transplant Rejection	Magenta Therapeutics, Inc.	Preclinical
89Zr-CD45 nanobody	CD45 Inhibitor \| PET Imaging	Diagnostic Radiopharmaceutical	Inflammation	Dana-Farber Cancer Institute, Inc.	Preclinical

(Data source: Synapse, as of October 16, 2025)

6. CUSABIO CD45 Research-Related Products

● CD45 (PTPRC) Recombinant Protein

Recombinant Human Receptor-type tyrosine-protein phosphatase C (PTPRC), partial (Active); CSB-MP019049HUc7

● CD45(PTPRC) Antibody

PTPRC Recombinant Monoclonal Antibody

CSB-RA019049MA1HU

CD45 (Apamistamab) Recombinant Monoclonal Antibody

CSB-RA019049MA2HU

References

[1] Barashdi, M., Ali, A., McMullin, M., & Mills, K. (2021). Protein tyrosine phosphatase receptor type C (PTPRC or CD45). Journal of Clinical Pathology, 74, 548 - 552.

[2] Rheinländer, A., Schraven, B., & Bommhardt, U. (2018). CD45 in human physiology and clinical medicine.. Immunology letters, 196, 22-32.

[3] Borowska, M., Liu, L., Caveney, N., et al. (2024). Orientation dependent CD45 inhibition with viral and engineered ligands. Science immunology, 9, eadp0707 - eadp0707.

[4] Dunlock, V., Arp, A., Singh, S.,et al. (2022). Tetraspanin CD53 controls T cell immunity through regulation of CD45RO stability, mobility, and function.. Cell reports, 39 13, 111006.

[5] Gil-Cantero, S., Puck, A., Künig, S., et al. (2025). The Soluble Cytoplasmic Tail of CD45 (ct-CD45) Regulates Dendritic Cell Activation and Function via TLR4 Signaling. International Journal of Molecular Sciences, 26.

[6] Lui, Y., Fernandes, J., Vuong, M., Sharma, S., et al. (2025). The Structural Biology of T‐Cell Antigen Detection at Close Contacts. Immunological Reviews, 331.

[7] Chang, V., Fernandes, R., Ganzinger, K., et al. (2016). Initiation of T cell signaling by CD45 segregation at ‘close-contacts’. Nature immunology, 17, 574 - 582.

[8] Kumar, V., Cheng, P., Condamine, T., et al. (2016). CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation.. Immunity, 44 2, 303-15.

[9] Park, S., Kim, J., Jang, G., et al. (2021). Aberrant activation of the CD45-Wnt signaling axis promotes stemness and therapy resistance in colorectal cancer cells. Theranostics, 11, 8755 - 8770.

[10] Ahmed, M., Limmer, A., & Hartmann, M. (2023). CD45RA and CD45RO Are Regulated in a Cell-Type Specific Manner in Inflammation and Sepsis. Cells, 12.

[11] Espinoza-Gutarra, M., Agarwal, P., Ferrer, L., et al. (2020). Relationship between CD45 Expression and Outcomes in B Lymphoblastic Leukemia/Lymphoma. Blood, 136, 24-24.

[12] Peng, Q., Zhu, B., Lu, Y., et al.(2023). Abstract 16746: Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis. Circulation.

[13] Alon, D., Paitan, Y., Robinson, E.,et al.(2021). Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide. Frontiers in Medicine, 8.

CD45: The Immune Cell "Gatekeeper" Protein – Why is it Emerging as a Novel Therapeutic Target?