Do We Need Full Donor Chimerism? How Alloreactive Cell Therapies without Substantial Engraftment Might Treat Hematologic Cancers

Current Drug Targets
Elizabeth F KrakowAnthony D Sung

Abstract

"Alloreactive cell therapy without substantial engraftment"; (ACT-WiSE) refers to adoptive transfer of natural ("non-engineered") human leukocyte antigen-mismatched lymphocytes to mediate anti-neoplastic alloreactivity in recipients without employing pharmacologic immunosuppression. By definition, ACT-WiSE entails subsequent rejection of most, if not all, donor cells. Macrochimerism is transient and microchimerism may be either short-lived or persistent. This strategy harnesses the anticancer potency of alloreactivity without incurring significant risk of graft-versus-host disease. "Microtransplantation" refers to a form of ACT-WiSE where the donor cell product contains hematopoietic progenitor cells. Microtransplantation therefore accelerates hematopoietic recovery and its immunomodulatory effects may differ from other forms of ACT-WiSE. Recent studies suggest that various forms of ACT-WiSE, including microtransplantation, may improve chemosensitivity in patients with myeloid malignancies, resulting in higher complete remission rates and increased survival. Microtransplantation has also demonstrated promising pilot results in relapsed or refractory Non-Hodgkin and Hodgkin lymphoma. ACT-WiSE and microtransplantation may establi...Continue Reading

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