In DepthBiomedicine

New cancer-fighting cells enter trials

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Science  14 Sep 2018:
Vol. 361, Issue 6407, pp. 1056-1057
DOI: 10.1126/science.361.6407.1056

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  • RE: New cancer-fighting cells enter trials
    • George Yizhou Tang, University of Cambridge, UK
    • Other Contributors:
      • Jovia Gao, University of Cambridge, UK

    The success of chimeric antigen receptors (CARs) in targeting T cells to tumors has inspired a new frontier in cancer research (1). This article discusses the advantages of expressing CARs in natural killer (NK) cells to enhance their innate anti-tumor activities, improve their specificity, and overcome the potentially fatal side-effects of CAR-T cell therapy (2). However, we must be careful not to overlook the limitations of CAR-NK cells.

    Unlike the two-signal model of T cell activation (3), NK cell activation is integrative in nature (4). It is uncertain how powerfully a CAR would overcome multiple inhibitory signals (5). In the context of the immunosuppressive tumor microenvironment (6), CAR-NK cells might therefore be less reliably activated than xenograft studies suggest (7, 8). Moreover, the short half-life of transfused CAR-NK cells results in declining cytotoxicity over time (9), which may select for resistance mutations in the target antigen, analogous to antibiotic resistance in bacteria.

    The challenges of acquiring NK cells cannot be trivialized. Immature NK cells, such as those derived from cord blood, have reduced cytotoxic function and carry the risk of malignant transformation (9, 10). To terminate their function, they must be modified with ‘suicide switches’, sensitive to specific drugs, which come with their own significant side effects (9). The mature lymphoma-derived NK-92 cell line has been favored for its superior in vitro anti-tumor cyto...

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    Competing Interests: None declared.
  • RE: Kill mosquitoes or dry the swamp? What is the best method for cure the cancer?
    • Mesut Tez, Surgical Oncologist, Ankara Numune Hospital

    Cancer is the one of the most important public health problem in recent years. [1]. The spending of hundreds of billions dollars that , the mortality rate of many cancers is at a level similar to that in 1930 or somewhat declining [1-3] Declining is largely a result of earlier detection. The observed trends may largely reflect changing incidence or earlier detection, rather than improved therapy[4]. We still do not have a valid hypothesis about carcinogenesis[3, 5]. Because of this, accumulation of large amounts of genomic data does not work in everyday clinical practice so far[3].
    In our routine clinical practice, we are trying to kill mosquitoes (cancer cells) to cure cancer. Sometimes we are using smart medications ( molecular-targeted therapies-it is look like, targeting the wings of mosquitoes ) or Chimeric antigen receptor T cells (killing mosquitoes with another insects). According to my 30 years clinical experience, these therapeutic approaches will not work. We need new therapeutic strategies (paradigm shift). Briefly,we must dry the swamp to cure cancer(fix the corrupted microenvironment) instead of killing mosquitoes.
    References
    1. Braun, E., The unforeseen challenge: from genotype-to-phenotype in cell populations. Reports on Progress in Physics, 2015. 78(3): p. 036602.
    2. Bailar, J.C. and H.L. Gornik, Cancer undefeated. New England Journal of Medicine, 1997. 336(22): p. 1569-1574.
    3. Brücher, B.L., et al., Imagine a world without...

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    Competing Interests: None declared.