Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge

被引:10
作者
de Witte, Moniek A. [1 ]
Kierkels, Guido J. J. [2 ]
Straetemans, Trudy [2 ]
Britten, Cedrik M. [3 ]
Kuball, Juergen [1 ,2 ]
机构
[1] Univ Med Ctr Utrecht, Dept Hematol, NL-3508 GA Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Lab Translat Immunol, NL-3508 GA Utrecht, Netherlands
[3] Johannes Gutenberg Univ Mainz TRON, Univ Med Ctr, Translat Oncol, Mainz, Germany
关键词
Allogeneic stem cell transplantation; Innate immune system; Gene therapy; CIMT; 2014; Phase I/II clinical trials; Regulatory authorities; MODIFIED T-CELLS; ACUTE MYELOID-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; CLINICAL-TRIALS; STEM-CELLS; NK CELLS; DONOR; THERAPY; ANTIGEN; BLOOD;
D O I
10.1007/s00262-015-1710-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Over half a century ago, the first allogeneic stem cell transplantation (allo-SCT) initiated cellular immunotherapy. For several decades, little progress was made, and toxicity of allo-SCT remained a major challenge. However, recent breakthroughs have opened new avenues to further develop this modality and to provide less toxic and equally efficient interventions for patients suffering from hematological or solid malignancies. Current novel cellular immune interventions include ex vivo expansion and adoptive transfer of tumor-infiltrating immune cells or administration of drugs which antagonize tolerizing mechanisms. Alternatively, transfer of immune cells engineered to express defined T cell receptors (TCRs) and chimeric antigen receptors (CARs) has shown its potential. A valuable addition to 'engineered' adaptive immunity has emerged recently through the improved understanding of how innate immune cells can attack cancer cells without substantial side effects. This has enabled the development of transplantation platforms with limited side effects allowing early immune interventions as well as the design of engineered immune cells expressing innate immune receptors. Here, we focus on innate immune interventions and their orchestration with TCR- and CAR-engineered immune cells. In addition, we discuss how the exploitation of the full potential of cellular immune interventions is influenced by regulatory frameworks. Finally, we highlight and discuss substantial differences in the current landscape of clinical trials in Europe as compared to the USA. The aim is to stimulate international efforts to support regulatory authorities and funding agencies, especially in Europe, to create an environment that will endorse the development of engineered immune cells for the benefit of patients.
引用
收藏
页码:893 / 902
页数:10
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