The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation

Xenotransplantation. 2023 May-Jun;30(3):e12802. doi: 10.1111/xen.12802. Epub 2023 Apr 7.

Abstract

The mechanistic/mammalian target of rapamycin (mTOR) is one of the systems that are necessary to maintain cell homeostasis, such as survival, proliferation, and differentiation. mTOR inhibitors (mTOR-Is) are utilized as immunosuppressants and anti-cancer drugs. In organ allotransplantation, current regimens infrequently include an mTOR-I, which are positioned more commonly as alternative immunosuppressants. In clinical allotransplantation, long-term efficacy has been established, but there is a significant incidence of adverse events, for example, inhibition of wound healing, buccal ulceration, anemia, hyperglycemia, dyslipidemia, and thrombocytopenia, some of which are dose-dependent. mTOR-Is have properties that may be especially beneficial in xenotransplantation. These include suppression of T cell proliferation, increases in the number of T regulatory cells, inhibition of pig graft growth, and anti-inflammatory, anti-viral, and anti-cancer effects. We here review the potential benefits and risks of mTOR-Is in xenotransplantation and suggest that the benefits exceed the adverse effects.

Keywords: Tregs; graft growth; immunosuppression; inflammation; mTOR inhibitor; neoplasia; viral infection; xenotransplantation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Immunosuppressive Agents* / pharmacology
  • Immunosuppressive Agents* / therapeutic use
  • Mammals
  • Sirolimus* / pharmacology
  • Sirolimus* / therapeutic use
  • Swine
  • T-Lymphocytes, Regulatory
  • TOR Serine-Threonine Kinases
  • Transplantation, Heterologous

Substances

  • Sirolimus
  • Immunosuppressive Agents
  • TOR Serine-Threonine Kinases