Cellular Immunotherapy: Using Alloreactivity to Induce Anti-Leukemic Responses without Prolonged Persistence of Donor Cells

Medical Sciences

Loren D. Fast¹  John Reagan² 

[1] Division of Hematology/Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, One Hoppin Street Coro West Suite 5.0.1, Providence, RI 02903, USA;Division of Hematology/Oncology, Warren Alpert School of Medicine at Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA; E-Mails:

关键词: alloreactivity;    haploidentical;    cellular immunotherapy;    donor cell infusion;   

DOI  :  10.3390/medsci1010037

来源: mdpi

【 摘 要 】

A goal of cancer immunologists is to harness cellular immune responses to achieve anti-cancer responses. One of the strongest activating stimuli for the immune system is the encounter with cells expressing allogeneic HLA molecules. While alloreactive responses can negatively impact of the outcome of hematopoietic stem cell transplant because of graft-versus-host disease (GVHD), these same responses can have anti-leukemic effects. Donor lymphocyte infusions have been used in an attempt to harness alloreactive responses to achieve anti-leukemic responses. Because this protocol is usually carried out in the absence of recipient anti-donor responses, this protocol often induces GVHD as well as anti-leukemic responses. A recent study indicated the infusion of large number of haploidentical donor cells (1–2 × 10⁸ CD3⁺ cells/kg) into patients with refractory hematological malignancies (100 cGy total body irradiation) resulted in 14 (7 major) responses/26 patients. A rapidly developing cytokine storm was observed, while no persisting donor cells could be detected at two weeks after infusion eliminating the possibility of GVHD. Characterization of the effector mechanisms responsible for the anti-leukemic responses in this protocol, should guide new approaches for achieving enhanced anti-leukemic responses using this protocol.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.