TROP2 Recombinant Monoclonal Antibody

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Description

Definition and Mechanism

TROP2 recombinant monoclonal antibodies are laboratory-engineered proteins designed to bind selectively to TROP2 epitopes. These antibodies are produced through recombinant DNA technology, ensuring high batch-to-batch consistency and reduced immunogenicity compared to traditional hybridoma-derived mAbs . Key mechanisms include:

  • Diagnostic detection: Flow cytometry, Western blot, and immunohistochemistry (IHC) for tumor profiling .

  • Therapeutic targeting: Enabling antibody-drug conjugates (ADCs), radioimmunotherapy (RIT), and chimeric antigen receptor T-cell (CAR-T) therapies .

Development and Engineering

The Cell-Based Immunization and Screening (CBIS) method has been pivotal in developing anti-TROP2 mAbs like TrMab-29 and TrMab-6 . This approach involves:

  • Immunization: Mice are immunized with TROP2-overexpressing CHO cells.

  • Hybridoma screening: Selection of clones with strong TROP2-specific binding via flow cytometry and Western blot .

  • Subclass optimization: IgG1 (TrMab-29) for diagnostic use vs. IgG2b (TrMab-6) for potential ADCC/CDC-mediated therapies .

AntibodySubclassApplicationsKey Findings
TrMab-29IgG1κFlow cytometry, Western blot, IHCDetects 40 kDa TROP2 band; glycosylation-independent epitope
TrMab-6IgG2bκFlow cytometry, IHC, Western blotDetects TROP2 in 93.4% of breast cancer specimens
JS108Humanized IgGPhase I clinical trial (NCT04601285)ADC targeting breast, lung, and gastric cancers

Characterization and Validation

  • Specificity: TrMab-29 and TrMab-6 show no cross-reactivity with TROP2-knockout cells (e.g., BINDS-29) .

  • Epitope analysis: TrMab-29 binds a glycan-independent epitope, enabling detection across glycosylation variants (Lec1/TROP2, Lec2/TROP2) .

  • Sensitivity: Commercial antibodies like ab253293 (Abcam) and MA5-46673 (Thermo Fisher) detect TROP2 at EC50 values as low as 0.73–1.08 ng/mL .

Clinical and Research Applications

  • Diagnostics: High concordance between IHC and molecular assays in breast cancer (93.4% positivity for TrMab-6) .

  • Therapeutic development:

    • ADCs: Sacituzumab govitecan (IMMU-132), an anti-TROP2-SN-38 conjugate, shows efficacy in triple-negative breast cancer (TNBC) .

    • Novel modalities: TrMab-29 is being explored for photoimmunotherapy (PIT) and CAR-T-cell therapy .

Therapy TypeExampleMechanismStatus
ADCIMMU-132SN-38 payload targeting TROP2+ cellsFDA-approved for TNBC
CAR-TExperimental constructsT-cell activation via TROP2 bindingPreclinical
Clinical TrialJS108 (NCT04601285)Tub196 conjugate for solid tumorsPhase I

Comparative Advantages

  • Multipurpose utility: TrMab-6 outperforms commercial mAbs (e.g., EPR20043, SP293) in non-fixed flow cytometry and IHC .

  • Structural insights: Antibodies like 2EF target the N-terminal TY domain of TROP2, disrupting dimerization and suppressing tumor growth .

Future Directions

  • Subclass engineering: Converting TrMab-29 to IgG2a/IgG2b for enhanced ADCC/CDC activity .

  • Dual-targeting strategies: Combining antibodies like 2EF and 2G10 to block TROP2 cleavage and dimerization .

  • Expanded clinical trials: Evaluating JS108 and similar ADCs in pancreatic and colorectal cancers .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Description

The TROP2 monoclonal antibody was generated by immunizing with recombinant human TROP2 protein. The gene encoding the TROP2 monoclonal antibody was cloned into a plasmid vector following sequencing of the cDNA. Transfection of the host cell with the plasmid vector containing the TROP2 monoclonal antibody gene was performed using a suitable method. The resulting TROP2 recombinant monoclonal antibody was purified using affinity chromatography, and its specificity was evaluated through ELISA. This TROP2 recombinant monoclonal antibody exhibited the ability to bind specifically to recombinant human TROP2 (CSB-MP023072HU1d7) with an EC50 range of 0.7284-1.075 ng/mL. It can react with human TROP2 protein.

TROP2, also known as TACSTD2, is a transmembrane glycoprotein expressed in various human tissues. It plays a significant role in cell adhesion, migration, and proliferation. TROP2 is involved in regulating cell growth and differentiation and has been demonstrated to be upregulated in numerous cancer types, including breast, colorectal, lung, and ovarian cancer. Overexpression of TROP2 is associated with tumor growth, metastasis, and unfavorable patient prognosis. Additionally, TROP2 has been recognized as a target for cancer immunotherapy.

Form
Liquid
Lead Time
Typically, we can dispatch the products within 1-3 working days after receiving your orders. Delivery time may vary depending on the purchasing method or location. Please consult your local distributors for specific delivery timeframes.
Synonyms
Cell surface glycoprotein Trop 2 antibody; Cell surface glycoprotein Trop-2 antibody; Cell surface glycoprotein Trop2 antibody; Epithelial glycoprotein 1 antibody; GA733 1 antibody; GA7331 antibody; M1S 1 antibody; M1S1 antibody; Membrane component chromosome 1 surface marker 1 antibody; Pancreatic carcinoma marker protein GA733 1 antibody; Pancreatic carcinoma marker protein GA733-1 antibody; Pancreatic carcinoma marker protein GA7331 antibody; TACD 2 antibody; TACD2_HUMAN antibody; TACSTD 2 antibody; Tacstd2 antibody; Trop 2 antibody; Trop2 antibody; Tumor associated calcium signal transducer 2 precursor antibody; Tumor-associated calcium signal transducer 2 antibody
Target Names
Uniprot No.

Target Background

Function
May function as a growth factor receptor.
Gene References Into Functions
  1. The results suggest that TROP2 expression could serve as an effective prognostic biomarker for oral squamous cell carcinoma. PMID: 30098828
  2. TROP-2, SLP-2, and CD56 were found to be effective diagnostic markers for PTC, particularly when used in combination. PMID: 29951933
  3. Trop2 exhibits a potential role in promoting EMT in BC. PMID: 29901160
  4. These findings indicate that TROP2 may promote osteosarcoma cell proliferation and migration via the PI3K/AKT signaling pathway, potentially serving as a novel therapeutic target for osteosarcoma. PMID: 29845216
  5. Downregulation of TACSTD2 is associated with hepatocellular carcinoma. PMID: 29538454
  6. These findings demonstrate that a membranous TROP-2 staining pattern is highly specific for PTC, potentially serving as a diagnostic marker aiding in the accurate classification of morphologically equivocal thyroid follicular-patterned lesions. PMID: 26862947
  7. TROP2 promoted the proliferation, migration, and metastasis of gallbladder cancer cells by regulating the PI3K/AKT pathway and inducing EMT. PMID: 28423362
  8. Clinical specimen analysis revealed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer. This study suggests that elevated expression of Trop2 may represent a significant molecular hallmark relevant to the progression of thyroid cancer. PMID: 28709407
  9. These results suggest a differential role for TROP2 in various lung cancer subtypes. PMID: 28404926
  10. Results indicate that TROP2 expression is upregulated in gastric tumors, and its co-expression with AREG protein is associated with TNM stage, tumor size, lymph node metastases, and distant metastases. PMID: 28256068
  11. Our findings suggest that Trop-2 expression is a robust predictor of tumor response to AKT inhibitors. They also support the identification of target-activatory pathways as efficient predictors of response in precision cancer therapy. PMID: 27022065
  12. Findings suggest that high TROP2 expression identifies distinct cell sub-populations in androgen-sensitive and androgen-independent prostate tumors. It may serve as a predictive biomarker for prostate cancer treatment response in androgen-sensitive tumors. PMID: 27283984
  13. TROP2 may play a crucial role in COPD by affecting basal cell function and thus airway remodeling through increased basal cell hyperplasia. PMID: 27887617
  14. TROP2 was overexpressed specifically in the majority of epithelial ovarian cancer and may be a novel prognostic biomarker. PMID: 27127000
  15. We compared the diagnostic value of TROP-2 expression in distinguishing between benign and malignant thyroid lesions to those of HBME-1, CK19, and galectin-3. PMID: 28547974
  16. TROP-2 membranous staining is a highly sensitive and specific marker for the classic and tall cell variants of papillary thyroid carcinoma, and for papillary microcarcinomas, with high overall specificity for papillary thyroid carcinoma. PMID: 27311870
  17. The results suggested that trop2 facilitated neovascularization of non-small-cell lung cancer via activating the ERK1/2 signaling pathway. PMID: 28345466
  18. We identified a homozygous TACSTD2 missense mutation, c.551A>G, p.(Tyr184Cys), in the affected family members. Both parents were heterozygous for the mutation, and unaffected siblings were either heterozygous or homozygous wild-type for this allele. PMID: 27227392
  19. Our results expand the mutational spectrum of TACSTD2 in patients with gelatinous drop-like corneal dystrophy (GDLD). PMID: 27149532
  20. Trop2 expression was higher in GC tissues compared to neighboring non-tumor tissues. Increased Trop2 protein levels in GC were associated with increased differentiation, tumor node metastasis stage, tumor size, lymph node metastasis, distant metastasis, and H. pylori infection. PMID: 26716416
  21. Trop-2 is a novel target for ADC therapy due to its high expression in many solid cancers. PMID: 26101915
  22. TROP2 is epigenetically downregulated and operates as a negative regulator of cell proliferation and migration in liver fluke-associated cholangiocarcinoma. PMID: 26626643
  23. TROP-2 is specifically expressed in papillary thyroid carcinoma. PMID: 26481593
  24. Overexpression of TROP2 appears to be an independent predictor of poor clinical outcome in nasopharyngeal carcinoma. PMID: 26617817
  25. Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples. PMID: 26600538
  26. TROP-2 can be used alongside HBME-1 in thyroid cytology to detect PTC. PMID: 25164548
  27. Our data suggest that TROP2 plays a significant role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease. PMID: 26773504
  28. TROP2 protein is expressed at high levels in colon cancer tissues. PMID: 26059528
  29. TACSTD2 protein, human, is predicting lymph node metastases in OSCC, overall survival, and disease-free survival. PMID: 24764155
  30. The amino acid exchange resulting from 4461T[C does not appear to alter binding of HO-3, suggesting that treatment with catumaxomab can be offered to patients regardless of their TACSTD1-genotype. PMID: 26115884
  31. These observations suggest that Trop2 serves an oncogenic role in LSCC and has potential as a therapeutic target. PMID: 25779928
  32. This study reveals that both EpCAM and Trop2 overexpression in pituitary adenomas correlate significantly with invasiveness and proliferation. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs. PMID: 25550831
  33. Trop2 loss triggers sensitivity to anti-ErbB3 antibodies, which results in reduced proliferation and tumorigenic growth of Trop2-negative head and neck squamous cell cancer cells. PMID: 25238142
  34. Studies have begun to identify the mechanisms underlying TROP2's functions, including regulated intramembrane proteolysis or specific interactions with integrin b1 and claudin proteins. PMID: 25523132
  35. We demonstrate that Trop-2 activation states are critical determinants of tumor progression and are powerful indicators of breast cancer patients' survival. PMID: 24824621
  36. Inhibition of Tacstd2 expression significantly inhibited chemotherapeutic reagent-induced apoptosis, and TACSTD2 regulated apoptotic gene expression through P63 containing the transactivation domain (TAp63). PMID: 24651436
  37. Trop2 is important in proliferation and apoptosis regulation in CaSki cells, which may become a novel target for cervical cancer treatment. PMID: 24816726
  38. Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating the ERK signaling pathway. PMID: 24086649
  39. miR-125b-1 causes mitogen-activated protein kinase pathway dysfunction through regulation of TACSTD2 expression. PMID: 23416980
  40. The results of this study suggest that TROP2 correlated with malignancy, proliferation, and angiogenesis in human gliomas. PMID: 23397225
  41. TROP2 gene expression can be used as an independent prognostic indicator for squamous cell carcinoma of the larynx. PMID: 22987366
  42. Sf9 cells were used to express the Trop2 ectodomain (Trop2EC) in two forms: wt glycosylated (gTrop2EC) and mutant non-glycosylated form (Trop2EC(Delta/N)). Recombinant protein was purified, and its structure was studied. PMID: 23872121
  43. Trop2 expression reflects a more malignant phenotype and may serve as an unfavorable prognostic factor for extranodal NK/T cell lymphoma, nasal type. PMID: 23979406
  44. The cells exhibited a low epithelial barrier function as well as decreased expression of tight-junction-related proteins claudin 1 and 7. PMID: 23868985
  45. This study shows that Trop-2 enhances directional prostate cancer cell migration through modulation of Rac1 GTPase activity. PMID: 23536555
  46. Network hubs and interacting partners are co-expressed with Trop-2 in primary human tumors, supporting a role of this signaling network in cancer growth. PMID: 22562244
  47. This study characterized the expression of TACSTD2 in invasive ductal breast cancer (IDC) and adjacent non-malignant tissues; studies demonstrated that the high expression of TACSTD2 correlates with a poor prognosis in IDC. PMID: 23031786
  48. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth. PMID: 22349828
  49. High expression of TROP2 was associated with stage IIb colon cancer. PMID: 23055188
  50. More than 90% of Gelatinous drop-like corneal dystrophy (GDLD) patients possessed the same haplotype with a Q118X mutation in TACSTD2. PMID: 23038033

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Database Links

HGNC: 11530

OMIM: 137290

KEGG: hsa:4070

STRING: 9606.ENSP00000360269

UniGene: Hs.23582

Involvement In Disease
Corneal dystrophy, gelatinous drop-like (GDLD)
Protein Families
EPCAM family
Subcellular Location
Membrane; Single-pass type I membrane protein.
Tissue Specificity
Placenta, pancreatic carcinoma cell lines.

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