Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies

E. Biagi, V. Marin, G. M. P. Giordano Attianese, E. Dander, G. D'Amico, A. Biondi
2007 Haematologica  
E ven though tumor immunotherapy is one of the most attractive and fascinating fields of modern medicine, clinical applications in humans have shown a limited number of significant responses and revealed many scientific and practical difficulties relating to the translation of apparently flawless in vitro or animal models to the setting of human cancers. [1] [2] [3] [4] Comprehension of the mechanisms of tumor escape represents one of the most relevant acquisitions in immunology and has opened
more » ... ogy and has opened a new challenge for scientists and physicians. 5,6 Tumor cells, in fact, evade recognition and elimination by immune effectors in many ways: i) low or absent expression of tumor-specific antigens; ii) expression of antigens that are shared with normal cells at certain developmental stages, so that the immune sys-tem has become self-tolerant or anergic; iii) down-regulation of surface expression of MHC molecules; iv) defective pathways of antigen processing and presentation; v) absence of appropriate co-stimulation to deliver a complete activation stimulus to effector T cells; vi) the presence of inhibitory molecules actively secreted by the tumor itself or by the tumor microenvironment (such as interleukin-10 and transforming growth factor-β); 7 and vii) the expansion of naturally occurring or tumorinduced T cells with regulatory activity. 8, 9 Besides being capable of efficiently overcoming these multiple mechanisms of immune escape, any application of immunotherapy must consider all the practical issues related to the production of immune cells for clinical use: i) the choice of the right antigen(s) to ensure use in a
doi:10.3324/haematol.10873 pmid:17339188 fatcat:6jttwpo5bzajlpnk73iwixasca