• Origin: The MC38 cell line is derived from C57BL/6 murine colon adenocarcinoma cells. The cell line is a commonly used murine model for colorectal carcinoma.
• Background Information: CD38 is widely expressed in hematopoietic and non hematopoietic cells and is an important marker of B cells. It is a potential target for multiple myeloma and autoimmune diseases.
• Gene targeting strategy: The exogenous promoter and human CD38, encoding the signal peptide, extracellular domain, transmembrane domain, and cytoplasmic region, were inserted to replace part of murine exon 3. The insertion disrupts the endogenous murine Cd38 gene, resulting in a non-functional transcript.
• Application: The B-hCD38 MC38 plus tumor models can be used for preclinical evaluation of monoclonal antibody drugs targeting human CD38.

CD38 expression analysis in B-hCD38 MC38 plus cells by flow cytometry. Single cell suspensions from wild-type MC38 and B-hCD38 MC38 plus cells cultures were stained with species-specific anti-mouse CD38 (Biolegend, 102707) and anti-human CD38 (Biolegend, 356606). Human CD38 was detected on the surface of B-hCD38 MC38 plus cells but not on wild-type MC38 cells. The 1-D10 clone of B-hCD38 MC38 plus cells was used for in vivo experiments.

Subcutaneous homograft tumor growth of B-hCD38 MC38 plus cells. B-hCD38 MC38 plus cells (5x10⁵) and wild-type MC38 cells (5x10⁵) were subcutaneously implanted into C57BL/6JNifdc 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 × long diameter × short diameter². As shown in panel A, B-hCD38 MC38 plus cells were able to establish tumors in vivo and can be used for efficacy studies.

B-hCD38 MC38 plus cells were subcutaneously transplanted into C57BL/6JNifdc mice (male, 7-week-old, n=6), and on 28 days post inoculation, tumor cells were harvested and assessed for human CD38 expression with anti-human CD38 (Biolegend, 356606) antibody by flow cytometry. As shown, human CD38 was highly expressed on the surface of tumor cells. Therefore, B-hCD38 MC38 plus cells can be used for in vivo efficacy studies of novel CD38 therapeutics.