B-hTROP2 mid MC38

NA • 311057

B-hTROP2 mid MC38

Catalog Number: 311057
Strain Name: NA
Strain Background: C57BL/6
Aliases: TACSTD2, EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1, TROP2, tumor associated calcium signal transducer 2, Trophoblast cell-surface antigen 2
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B-hTROP2 mid MC38

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  • Description
  • Targeting strategy
  • Phenotypic analysis
  • Efficacy

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      Description

      The mouse Trop2 gene was replaced by human TROP2 coding sequence in B-hTROP2 mid MC38 cells. Human TROP2 is highly expressed on the surface of B-hTROP2 mid MC38 cells.

      Targeting strategy

      The exogenous promoter and human TROP2 coding sequence was inserted to replace part of murine exon 1. The insertion disrupts the endogenous murine TROP2 gene, resulting in a non-functional transcript.

      TROP2 Protein Expression Analysis in B-hTROP2 MC38 Cells by Flow Cytometry

      Single cell suspensions from wild-type MC38 and B-hTROP2 mid MC38 cultures were stained with species-specific anti-TROP2 antibody. Human TROP2 was detected on the surface of B-hTROP2 mid MC38 cells but not wild-type MC38 cells. The 2-B04 clone of B-hTROP2 mid MC38 cells was used for in vivo tumor growth assays.

      Subcutaneous homograft tumor growth of B-hTROP2 mid MC38 cells

      B-hTROP2 mid MC38 cells (5x105) and wild-type MC38 cells (5x105) were subcutaneously implanted into heterozygous B-hTROP2 mice (female, 7-week-old, n=5).Tumor volume and body weight were measured twice a week. (A) Average tumor volume ± SEM. (B) Body weight (Mean± SEM). Volume was expressed in mm3 using the formula: V=0.5 X long diameter X short diameter2. As shown in panel A, B-hTROP2 mid MC38 cells were able to form tumors in vivo and can be used for efficacy studies.

      Note that B-hTROP2 mid MC38 cells successfully formed tumors only in B-hTROP2 mice, but not in wild-type mice.

      B-hTROP2 mid MC38 tumor cells growth of individual mice

      B-hTROP2 mid MC38 cells (5x105) and wild-type MC38 cells (5x105) were subcutaneously implanted into heterozygous B-hTROP2 mice (female, 7-week-old, n=5). As shown in panel, B-hTROP2 mid MC38 cells were able to establish tumors in vivo and can be used for efficacy studies.

      TROP2 In Vivo Expression Analysis: Validation of B-hTROP2 MC38 Tumor Models

      B-hTROP2 mid MC38 cells were subcutaneously transplanted into heterozygous B-hTROP2 mice (n=5), and on 35 days post inoculation, tumor cells were harvested and assessed for human TROP2 expression by flow cytometry. As shown, human TROP2 was highly expressed on the surface of tumor cells. Therefore, B-hTROP2 mid MC38 cells can be used for in vivo efficacy studies of TROP2 therapeutics.

      Note that B-hTROP2 mid MC38 cells successfully formed tumors only in B-hTROP2 mice, but not in wild-type mice.

      Tumor growth curve & Body weight changes

      Subcutaneous homograft tumor growth of B-hTROP2 mid MC38 cells.

      B-hTROP2 mid MC38 cells (5x105, 1x106, 5x106) and wild-type MC38 cells (5x105) were subcutaneously implanted into homozygous B-hTROP2 mice (female, 7-week-old, n=6). Tumor volume and body weight were measured twice a week. (A) Average tumor volume ± SEM. (B) Body weight (Mean± SEM). Volume was expressed in mm3 using the formula: V=0.5 X long diameter X short diameter2. As shown in panel A, B-hTROP2 mid MC38 cells were able to form tumors in vivo and can be used for efficacy studies.

      Note that B-hTROP2 mid MC38 cells successfully formed tumors only in B-hTROP2 mice , but not in wild-type mice.

      B-hTROP2 mid MC38 tumor cells growth of individual mice

      B-hTROP2 mid MC38 cells (5x105, 1x106, 5x106) and wild-type MC38 cells (5x105) were subcutaneously implanted into homozygous B-hTROP2 mice (female, 7-week-old, n=6). As shown in panel, B-hTROP2 mid MC38 cells were able to establish tumors in vivo and can be used for efficacy studies.

      Note that B-hTROP2 mid MC38 cells successfully formed tumors only in B-hTROP2 mice , but not in wild-type mice.

      Human TROP2 Protein Expression Analysis in B-hTROP2 MC38 Tumor Cells

      B-hTROP2 mid MC38 cells were subcutaneously transplanted into homozygous B-hTROP2 mice (female, 7-week-old, n=6), and on 35 days post inoculation, tumor cells were harvested and assessed for human TROP2 expression by flow cytometry. As shown, human TROP2 was highly expressed on the surface of tumor cells. Therefore, B-hTROP2 mid MC38 cells can be used for in vivo efficacy studies of TROP2 therapeutics.

      Note that B-hTROP2 mid MC38 cells successfully formed tumors only in B-hTROP2 mice, but not in wild-type mice.

      In vivo Efficacy of anti-human TROP2 antibody-drug conjugate (ADC)
      • Anti-human TROP2 ADC Datopotamab Deruxtecan (in-house) was efficacious in controlling tumor growth in B-hTROP2 mice, demonstrating that the B-hTROP2 mice provide a powerful preclinical model for in vivo evaluation of anti-human TROP2 ADC.

      Establishment of a MC38 model in B-hTROP2 mice and in vivo efficacy study of anti-human TROP2 antibody-drug conjugate (Datopotamab Deruxtecan, in house). Murine colon cancer B-hTROP2 mid MC38 cells (Cat # 311057) were subcutaneously implanted into homozygous B-hTROP2 mice (female, 7-8-week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm3, at which time they were intravenously injected with anti-human TROP2 ADC Datopotamab Deruxtecan (in-house) as indicated in panel.

      (A) Tumor growth curves. (B) Body weight changes during treatment In vivo. (C) In vivo efficacy of anti-human TROP2 ADC - individual tumor growth curves. Values are expressed as mean ± SEM.