Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a Phase I clinical study

被引：89

作者：

Barkholt, L. ^{[1
]}

Alici, E. ^{[1
]}

Conrad, R. ^{[1
]}

Sutlu, T. ^{[1
]}

Gilljam, M. ^{[1
]}

Stellan, B. ^{[1
]}

Christensson, B. ^{[1
]}

Guven, H. ^{[1
]}

Bjorkstrom, N. K. ^{[1
]}

Soderdahl, G. ^{[1
]}

Cederlund, K. ^{[1
]}

Kimby, E. ^{[1
]}

Aschan, J. ^{[1
]}

Ringden, O. ^{[1
]}

Ljunggren, H-G ^{[1
]}

Dilber, M. S. ^{[1
]}

机构：

[1] Karolinska Univ Hosp, SE-14186 Stockholm, Sweden

来源：

IMMUNOTHERAPY | 2009年 / 1卷 / 05期

基金：

瑞典研究理事会;

关键词：

cellular immunotherapy; donor lymphocyte infusion; ex vivo expansion; hematopoietic stem cell transplantation; NK cell; NK-like T cell; NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; EFFECTOR-CELLS; TRANSPLANTATION; EXPANSION; GRAFT;

D O I：

10.2217/IMT.09.47

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of g raft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum alpha-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.

引用

页码：753 / 764

页数：12

共 39 条

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