CD147 blockade as a potential and novel treatment of graft rejection

Abstract

Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody-based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one-way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one-way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody-treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)-17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs.

Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

“…Recently, an agent against CD147, called ABX-CBL (gavilimomab, a hybridoma-generated murine IgM monoclonal antibody), has been proposed to specifically inhibit graft rejection after CD147 blockade was tested for the treatment of steroid-resistant acute GVHD 67 .…”

Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging

“…CD147 is widely expressed in many tissues, including the lung. In the lung, it is highly expressed in primary human bronchial epithelial cells. , This may be one of the reasons for the high uptake of 131 I-meplazumab in the lung. The in vivo distribution of 131 I-meplazumab was consistent with CD147 as can be seen from the biodistribution and SPECT imaging results.…”

A Bioelectromagnetic Proposal Approaching the Complex Challenges of COVID-19

“…BSG regulates cell proliferation, apoptosis, migration, metastasis, and differentiation of tumor cells, especially under hypoxic conditions [160]. Inhibition of the BSG protein prevents interleukin IL-17 and CD4+ and CD8+ memory T-cells in the peripheral circulation [161]. The activity of BSG (CD147) increases under hypoxic conditions [160], which is usually generated by the massive use of ATP for cellular viral infection.…”