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The therapeutic potential of immune cell-derived exosomes as an alternative to adoptive cell transfer

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초록

Adoptive cell transfer (ACT), a form of cell-based immunotherapythat eliminates cancer by restoring and strengthening thebody’s immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident orperipheral blood-modified immune cells into cancer patientsto mediate anti-tumor response. Although these immune cellscontrol and eradicate cancer via enhanced cytotoxicity againstspecific tumor antigens, several side effects have been frequentlyreported in clinical trials. Recently, exosomes, potential cellfreetherapeutics, have emerged as an alternative to cell-basedimmunotherapies, due to their higher stability under same storagecondition, lower risk of GvHD and CRS, and higher resistanceto immunosuppressive tumor microenvironment. Exosomes,which are nano-sized lipid vesicles, are secreted by living cells,including immune cells. Exosomes contain proteins, lipids,and nucleic acids, and the functional role of each exosome isdetermined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cellsand NK cells exert anti-tumor effects via proteins such asgranzyme B and FasL. In this mini-review, we describe thecurrent understanding of the ACT and immune cell-derivedexosomes and discuss the limitations of ACT and the opportunitiesfor immune cell-derived exosomes as immune therapies.

Abstract

Adoptive cell transfer (ACT), a form of cell-based immunotherapythat eliminates cancer by restoring and strengthening thebody’s immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident orperipheral blood-modified immune cells into cancer patientsto mediate anti-tumor response. Although these immune cellscontrol and eradicate cancer via enhanced cytotoxicity againstspecific tumor antigens, several side effects have been frequentlyreported in clinical trials. Recently, exosomes, potential cellfreetherapeutics, have emerged as an alternative to cell-basedimmunotherapies, due to their higher stability under same storagecondition, lower risk of GvHD and CRS, and higher resistanceto immunosuppressive tumor microenvironment. Exosomes,which are nano-sized lipid vesicles, are secreted by living cells,including immune cells. Exosomes contain proteins, lipids,and nucleic acids, and the functional role of each exosome isdetermined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cellsand NK cells exert anti-tumor effects via proteins such asgranzyme B and FasL. In this mini-review, we describe thecurrent understanding of the ACT and immune cell-derivedexosomes and discuss the limitations of ACT and the opportunitiesfor immune cell-derived exosomes as immune therapies.

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