Human MICA Stable Cell Line - MC38

Antigen-peptide-based mRNA vaccines have been explored for the immunotherapy of various cancer types due to their advantages in eliciting durable and specific immune responses; however, their role in regulating tumor metastasis remains unclear. Here, researchers identified a peptide-Ma3P-based on a conserved linear epitope located within the proteolytic cleavage site region of the α3 domain of MHC Class I-related chain A (MICA). Building upon this, they designed an mRNA vaccine, mCM10-L, which encodes the carrier protein CRM197 and 10 tandem repeats of the Ma3P sequence. The study demonstrated that vaccination with mCM10-L induces the production of specific antibodies, thereby blocking the shedding of the MICA/B α1/2 domains, activating CD8+ T cells and natural killer (NK) cells, and significantly inhibiting the metastasis of MICA/B-positive tumors in mice. Furthermore, in in vitro co-culture human organoid models and humanized mouse models, stimulation with mCM10-L triggered the generation of specific antibodies, which subsequently enhanced MICA/B-mediated immune killing effects. These findings highlight the potential clinical utility of the mCM10-L vaccine.

To investigate whether specifically blocking the shedding of MICA/B α1/2 via MIA-2 could inhibit tumor metastasis, researchers established a pulmonary metastasis model in C57BL/6 mice using EGFP+MICA+ MC38 cells. Although the mouse genome lacks MICA/B genes, human MICA/B α1/2 typically activates murine NKG2D. Intraperitoneal administration of MIA-2 significantly reduced pulmonary metastatic lesions in the mice, increased the surface expression levels of MICA/B α1/2 on metastatic EGFP+ tumor cells, and decreased serum concentrations of sMICA/B (Figure 1H-1J). Researchers obtained identical results in a pulmonary metastasis model established using EGFP+MICA+ murine melanoma B16-F10 cells (Figure 1K-1M). These data indicate that targeted blockade of MICA/B α1/2 shedding can inhibit the metastasis of MICA/B+ tumor cells.

Figure 1. Blocking the shedding of MICA/B α1/2 inhibited the metastasis of MICA/B+ tumor cells. (Wang R, et al., 2025)