Adoptive allogeneic cell-mediated immunotherapy and nonmyeloablative stem-cell transplantation

Shimon Slavin, Shoshana Morecki, Elizabeth Naparstek, Arnon Nagler, Gabor Varadi, Rami Ben-Yosef, Reuven Or

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Allogeneic blood or marrow transplantation (alloBMT) is currently the most effective modality for the eradication of hematologic malignancies in patients at high risk for relapse or resistant to conventional chemoradiotherapeutic approaches. High-dose myeloablative chemoradiotherapy may also be supported by autologous stem-cell transplantation. However, the risk of relapse is higher in the absence of an allogeneic graft-versus-leukemia (GVL) effect [1]. A number of approaches to improve antitumor effects induced by donor T cells have been developed, including reduction or avoidance of posttransplant immunosuppression [2-5]. However, this approach is hazardous since recipients of fully or partially matched allografts may develop lethal GVHD. Allogeneic cell-mediated immunotherapy (alloCT) using donor lymphocyte transfusion (DLT) in graded increments is safer because it permits some control of GVHD [6,7]. We and others have shown that the risk of GVHD decreases with increasing intervals between the transplant and DLT [7-10]. Because of the time-interval effect, it is sometimes possible to provoke a marked GVL response with a large number of lymphocytes without causing severe GVHD. Furthermore, we have recently shown that host-type tumor cells resistant to DLT may still respond to unstimulated or in vitro activated lymphocytes in conjunction with a short course of intermediate-dose IL-2 [6]. The therapeutic action of DLT with or without IL-2 may not require durable engraftment of donor lymphocytes. In mice inoculated with 6 106 B-cell leukemia/lymphoma cells of BALB/c origin, eradication of host-type leukemia cells occurs within 2-3 weeks following DLT with T cells fully tolerant to host antigens. In vivo activation of the same effector cells with rIL-2 can eradicate the leukemia in 3-5 days [11]. As previously mentioned, the same strategy has been applied in a cohort of patients with a variety of hematologic malignancies relapsing after allogeneic BMT [6]. It therefore appears that alloCT in conjunction with rIL-2 activation of T cells can be an effective method of treating or preventing relapse [7,12].

Original languageEnglish
Title of host publicationAllogeneic Immunotherapy for Malignant Diseases
PublisherCRC Press
Pages255-266
Number of pages12
ISBN (Electronic)9780203909508
ISBN (Print)9780824767815
StatePublished - 1 Jan 2000
Externally publishedYes

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