HAVCR2 Antibody

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Description

Definition and Purpose of HAVCR2 Antibodies

HAVCR2 antibodies are recombinant monoclonal antibodies engineered to bind specifically to the HAVCR2/TIM-3 protein. These antibodies are used to:

  • Detect HAVCR2 expression in immune cells (e.g., T cells, NK cells, macrophages) via flow cytometry or immunohistochemistry .

  • Block HAVCR2-ligand interactions (e.g., galectin-9, phosphatidylserine) to study immune regulation .

  • Support therapeutic development by targeting TIM-3 in combination with PD-1/PD-L1 inhibitors to overcome immunotherapy resistance .

Key Findings from Studies

  • Cancer Immunotherapy:

    • HAVCR2 is upregulated in PD-1-resistant tumors (e.g., melanoma, lung adenocarcinoma). Dual blockade of HAVCR2 and PD-1 restores T-cell function and improves antitumor responses .

    • Anti-HAVCR2 antibodies (e.g., LY3321367, MBG453) are in phase 1/2 trials for solid and hematologic malignancies .

  • Immune Cell Regulation:

    • HAVCR2 antibodies inhibit TIM-3-mediated suppression of NK cells, enhancing cytotoxicity in esophageal cancer and melanoma models .

    • In chronic viral infections, TIM-3 blockade reverses CD8+ T-cell exhaustion .

  • Pan-Cancer Analysis:

    • HAVCR2 mRNA is overexpressed in 21 cancer types (e.g., glioblastoma, renal cell carcinoma) and correlates with poor prognosis .

    • High HAVCR2 expression associates with increased immune infiltration (B cells, dendritic cells) in tumors like SKCM and UVM .

Experimental Use Cases

  • Immune Profiling:
    Paired antibodies (e.g., MP01083-2: 84183-4-PBS capture + 84183-3-PBS detection) enable quantitative analysis of soluble TIM-3 in serum via sandwich ELISA .

  • Mechanistic Studies:
    Antibodies validate TIM-3's role in HMGB1-mediated nucleic acid sensing and CEACAM1-dependent T-cell tolerance .

  • Therapeutic Screening:
    Used to assess TIM-3/PD-1 co-blockade efficacy in preclinical models of melanoma and AML .

Challenges and Future Directions

  • Biomarker Validation:
    Despite HAVCR2's prognostic value in cancers like glioblastoma, standardized assays for clinical use are lacking .

  • Combination Strategies:
    Ongoing trials aim to optimize dosing and timing of anti-HAVCR2 antibodies with existing immunotherapies .

Product Specs

Buffer
PBS with 0.02% Sodium Azide, 50% Glycerol, pH 7.3. Store at -20°C. Avoid freeze/thaw cycles.
Lead Time
Typically, we can ship products within 1-3 business days after receiving your order. Delivery times may vary depending on the purchase method or location. Please contact your local distributor for specific delivery timelines.
Synonyms
CD366 antibody; FLJ14428 antibody; HAVcr-2 antibody; Havcr2 antibody; HAVR2_HUMAN antibody; Hepatitis A virus cellular receptor 2 antibody; Kidney injury molecule 3 antibody; KIM 3 antibody; KIM3 antibody; T cell immunoglobulin and mucin domain containing 3 antibody; T cell immunoglobulin mucin 3 antibody; T-cell immunoglobulin and mucin domain-containing protein 3 antibody; T-cell immunoglobulin mucin family member 3 antibody; T-cell immunoglobulin mucin receptor 3 antibody; T-cell membrane protein 3 antibody; Tim 3 antibody; TIM-3 antibody; TIM3 antibody; TIMD-3 antibody; TIMD3 antibody
Target Names
Uniprot No.

Target Background

Function
HAVCR2 antibody is directed against the cell surface receptor known as TIM-3 (T-cell immunoglobulin and mucin domain-3). This receptor plays a crucial role in modulating both innate and adaptive immune responses, generally exhibiting an inhibitory function. While reports suggest stimulatory functions under certain cellular contexts or with specific ligands, its primary role is considered inhibitory. TIM-3 regulates macrophage activation and exerts a suppressive effect on T-helper type 1 lymphocyte (Th1)-mediated autoimmune and alloimmune responses, promoting immunological tolerance. In CD8+ cells, TIM-3 attenuates TCR-induced signaling by inhibiting NF-κB and NFAT promoter activities, leading to reduced IL-2 secretion. This function may be linked to its association with LCK, potentially hindering phosphorylation of TCR subunits, or LGALS9-dependent recruitment of PTPRC to the immunological synapse. However, TIM-3 has also been demonstrated to activate TCR-induced signaling in T-cells, possibly involving ZAP70, LCP2, LCK, and FYN. When expressed on regulatory T (Treg) cells, TIM-3 can suppress Th17 cell responses. TIM-3 serves as a receptor for LGALS9, and binding to this ligand is believed to result in the suppression of T-cell responses. This suppression may be mediated by the induction of apoptosis in antigen-specific cells, potentially involving HAVCR2 phosphorylation and disruption of its association with BAG6. The interaction between TIM-3 and LGALS9 is also proposed to contribute to the innate immune response to intracellular pathogens. Expressed on Th1 cells, TIM-3 interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages, stimulating antibactericidal activity, including IL-1β secretion, and restricting intracellular bacterial growth. However, the function of TIM-3 as a receptor for LGALS9 has been challenged. TIM-3 has also been reported to enhance CD8+ T-cell responses to acute infections, such as those caused by Listeria monocytogenes. TIM-3 acts as a receptor for phosphatidylserine (PtSer), and this binding is calcium-dependent. This interaction may allow TIM-3 to recognize PtSer on apoptotic cells, leading to their phagocytosis. TIM-3 mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, TIM-3 promotes conjugation but not engulfment of apoptotic cells. On dendritic cells (DCs), TIM-3 positively regulates innate immune responses and, in synergy with Toll-like receptors, promotes the secretion of TNF-α. In tumor-infiltrating DCs, TIM-3 suppresses nucleic acid-mediated innate immune responses by interacting with HMGB1, interfering with nucleic acid sensing and the trafficking of nucleic acids to endosomes. On natural killer (NK) cells, TIM-3 acts as a coreceptor to enhance IFN-γ production in response to LGALS9. However, TIM-3 has also been shown to suppress NK cell-mediated cytotoxicity, negatively regulating NK cell function during LPS-induced endotoxic shock.
Gene References Into Functions
  1. TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors PMID: 29316433
  2. TIM-3 and IL-37 may be used as potential biomarkers of active rheumatoid arthritis. PMID: 30106887
  3. High TIM3 expression is associated with gastric cancer. PMID: 30106451
  4. miR-498 can effectively suppress TIM-3 expression in the acute myeloid leukemia cell line PMID: 30107988
  5. These results indicate that TIM-3 may be involved in the pathogenesis of immune thrombocytopenia which subsequently can represent an opportunity for new therapeutic plan, moreover. This may have a prognostic value for disease severity. PMID: 28974109
  6. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines and their intratumoral infiltration correlates with a bad prognosis. Tim-3 appeared as a potential biomarker of anti-PD-1 resistance. Combined blockade of PD-1 and Tim-3 axis demonstrated potent clinical efficacy in preclinical models and reinforced the rationale of using an anti-Tim-3 to override tumor resistance.[review] PMID: 29547109
  7. this study shows that TIM-3 expression identifies a distinctive PD-1(+) follicular helper T cell subset, with reduced interleukin 21 production and B cell help function in ovarian cancer patients PMID: 29482158
  8. TIM-3 high expression rate was an independent prognostic factor for extranodal NK/T cell lymphoma, nasal type PMID: 28901003
  9. sTim-3 is a promising biomarker for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in kidney transplantation recipients PMID: 29310109
  10. The expression of Tim-3 on CD14+ monocytes is involved in systemic inflammatory reaction after intracerebral hemorrhage. PMID: 29310959
  11. TIM-3 gene may play an important role as a genetic risk factor for the progression and prognosis of invasive breast cancer. PMID: 29263040
  12. Tim-3(+) NK cells had decreased capability of IFN-r secretion, while Tim-3(+) monocytes showed a M2-like phenotype. Importantly, Tim-3 level on both NK cells and monocytes positively correlated with the ratio of Ki-67(+) tumor cells. PMID: 29174343
  13. T-cell immunoglobulin mucin-3/galectin-9 (Tim-3/Gal-9) binding signaling can also engage other binding partners to induce distinct cellular responses [Review]. PMID: 29027155
  14. Polymorphism +4259A>C in exon 3 of the TIM-3 gene is associated with susceptibility to multiple sclerosis but polymorphism -1637C>T in the promoter region of TIM-1 is not. PMID: 29141799
  15. The interaction between Gal-9/TIM-3 pathway and follicular helper cells contributed to viral persistent in chronic hepatitis C virus infection. PMID: 28772217
  16. Exosomal total protein, Tim-3 and Galectin-9 were up-regulated in non-small cell lung cancer plasma. PMID: 29452091
  17. the monitoring of sTim3 in urine may be a novel and promising noninvasive approach for the detection of AR. Furthermore, measurement of sTim3 in urine may contribute to predict the response to antirejection therapy and a poor outcome following AR. PMID: 28586044
  18. the CD4(+)CD25(+)Foxp3(+) Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner. PMID: 28478516
  19. our study highlights the role of TIM-3 as a potential prognostic marker and a promising therapeutic target in solid tumors. PMID: 28423646
  20. HAVCR2 regulates cytokines, chemokines, prostaglandins and cell adhesion molecules in the presence of viral infection, which suggests a potential for HAVCR2 activators as therapeutics for the management of preterm birth associated with viral infections. PMID: 28466996
  21. serum levels may be increased in patients with early phase diffuse cutaneous systemic sclerosis and associated with cardiac involvement and renal crisis PMID: 27651303
  22. Preoperative Tim3 expression on peripheral NK cells is correlated with differential staging in colorectal cancer, and may be useful as a serum biomarker. PMID: 28440449
  23. TIM-3 polymorphism is associated with response to therapy in hepatitis B virus-related hepatocellular carcinoma. PMID: 27034168
  24. BMI-1, TIM-3 and CLL-1 have roles in acute myeloid leukemia prognosis and therapy PMID: 27506934
  25. Quantification of TIM-3 and KIM-1 mRNA expressions, along with KIM-1 protein measurements in urine and blood could be employed as promising tools for noninvasive diagnosis of allograft dysfunction. PMID: 28757398
  26. Results show that human acute myeloid leukemia (AML) cells possess a secretory pathway which leads to the production and release of soluble Tim-3 and galectin-9. Both proteins prevent the activation of NK cells and impair their AML cell-killing activity. PMID: 28750861
  27. after 14 days of glucocorticoid therapy, clinical findings (serum bilirubin, skin GVHD) and plasma biomarkers (TIM3, ST2, sTNFR1) can predict failure of GVHD treatment and nonrelapse mortality. PMID: 28478120
  28. These findings suggested that rs10053538 in TIM-3 might increase susceptibility to and promote the progression of breast cancer in Chinese women PMID: 27248321
  29. Results indicate that T cell Ig and mucin domain 3 protein (TIM-3) polymorphisms (-1516G/T, -574G/T, and +4259T/G) were associated with the increased risk of cancer in Chinese Han population. PMID: 27008699
  30. In cultured MART1-specific CD8 T cells stimulated with peptide-loaded artificial antigen-presenting cells, anti-TIM-3 antibody treatment promotes generation of effector T cells, with acquisition of an activated phenotype, increased cytokine production, enhanced proliferation, and a transcription program associated with T cell differentiation. Anti-TIM-3 drives CD8 T cell differentiation through activation of mTORC1. PMID: 29127145
  31. Our results show that Tim-3 is a critical negative regulator of NLRP3 inflammasome and provides a potential target for intervention of diseases with uncontrolled inflammasome activation. PMID: 28799242
  32. soluble Tim-3 might play inhibitory roles in impaired Tim-3-mediated clearance of apoptotic cells in systemic lupus erythematosus. PMID: 28754800
  33. We found a novel mechanism through which Tim-3 could suppress antitumor immunity by utilizing the suppression of CD4(+) follicular helper cells (Tfh) function and provide new insight in the regulation of Tfh cells in breast cancer patients PMID: 27156907
  34. Tim3/Gal-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-kappaB signaling pathway. PMID: 28756232
  35. this study shows that severe aplastic anemia untreated patients have lower TIM-3 expression on NK cells and CD56dim NK subsets compared with normal controls, and are correlated with the severity of pancytopenia of SAA PMID: 28637584
  36. We conclude that Tim-3 is a biomarker of dysfunctional plasmacytoid dendritic cells PMID: 28264968
  37. The present study defines the minimal TIM-3 promoter region and demonstrates its interaction with c-Jun during TIM-3 transcription in CD4(+) T cells. PMID: 27243212
  38. Our findings establish intratumoral Tim-3(+)PD1(+)CD8(+) T cells as critical mediators of an aggressive phenotype in RCC. PMID: 27872087
  39. Osteosarcoma patients with higher Tim-3 had relatively lower survival. Multivariate analyses for overall survival revealed that high serum soluble Tim-3 level was an independent prognostic factor for osteosarcoma PMID: 28671022
  40. urther analyses revealed that the levels of Tim-3 on CD4+ T cells and CD8+ T cells exhibited different expression patterns in terms of localization depending on pathological category of prostate cancer and metastasis. Immunohistochemical analysis revealed that positive staining of Tim-3 in prostate cancer but little or no staining of Tim-3 was observed in benign prostate hyperplasia epithelium. PMID: 28681697
  41. this review discusses the recent findings on Tim-3, the role it plays in regulating immune responses in different cell types and the rationale for targeting Tim-3 for effective cancer immunotherapy PMID: 28258697
  42. The -1516G > T, -574G > T and +4259T > G SNPs within TIM-3 gene might play an important role as a genetic risk factor in the pathogenesis of ET. PMID: 27990849
  43. this study shows that that Tim-3 expression defines a subpopulation of PD-1+ exhausted NY-ESO-1-specific CD8+ T cell and PD-1+Tim-3+ CD8+ T cells represented the largest subset of NY-ESO-1-specific CD8+ T cells in gastric cancer patients PMID: 28110884
  44. Increased TIM3+CD8+T cells with lower perforin and granzyme B expression and higher CD95 expression in MDS patients had been observed. These findings suggested that TIM3 might be related to CD8+T cells defect. PMID: 27846431
  45. our results suggested that PD-1 and TIM-3 blockade might be necessary in developing effective immunotherapeutic strategies in malignant Schwannoma, in which TIM-3 may play a more important role. PMID: 28475007
  46. these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4(+) T cells PMID: 28466780
  47. In conclusion, Tim-3 on immune cells negatively regulates cell-mediated immunity against Plasmodium infection, and blocking Tim-3 signaling enhances sterile immunity and may play a protective role during malarial parasite infections. PMID: 27638944
  48. this study shows that the transcription factor T-bet controls Tim-3-mediated inhibition of monocyte/macrophage function during chronic hepatitis C virus infection PMID: 27809352
  49. this study shows that TIM-3 expressed on myeloid leukaemia cells may facilitate functional exhaustion in T helper cells PMID: 27565576
  50. this study shows that in osteosarcoma patients, Tim3 expression did not directly mediate immune suppression, but the interaction between Tim3+ T cells and monocytes, naive CD4+ T cells, and Gal9-expressing CD4+ CD25+ Tregs could resulting in progressive suppression of Th1 responses PMID: 28103502

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Database Links

HGNC: 18437

OMIM: 606652

KEGG: hsa:84868

STRING: 9606.ENSP00000312002

UniGene: Hs.710500

Involvement In Disease
May be involved in T-cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV).
Protein Families
Immunoglobulin superfamily, TIM family
Subcellular Location
Membrane; Single-pass type I membrane protein. Cell junction. Cell membrane.
Tissue Specificity
Expressed in T-helper type 1 (Th1) lymphocytes. Expressed on regulatory T (Treg) cells after TCR stimulation. Expressed in dendritic cells and natural killer (NK) cells. Expressed in epithelial tissues. Expression is increased on CD4+ and CD8+ T-cells in

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