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  • Introduction Cancer therapy has evolved throughout the decad

    2019-06-12

    Introduction Cancer therapy has evolved throughout the decades and is beginning to branch off into new and exciting fields including immunotherapy. The hope of this new field stems from the lack of success of chemotherapy in general. Chemotherapy\'s cytotoxic characteristics were regarded as one of three major methods of treating cancer. The other two methods include surgery and radiation. Due to a vast misunderstanding of the role of chemotherapy in late stage cancer, the likelihood of a full recovery from terminal cancer is close to zero [1]. Advances in genomics to aid in electing effective chemotherapeutic agents increased the success rate of cancer treatments, particularly when cancer has become metastatic [2]. Biomarkers are molecular characteristics of biological functions that can be readily measured or detected to determine cellular or physiological functions. Cancer biomarkers used in cancer research and treatment utilize this information to inform physicians and researchers of targets for chemotherapy in particular and can even be used to measure the effectiveness of treatments in some circumstances. Many forms of immunotherapy have been proposed over the years. These immunotherapies range from checkpoint therapy [3], cancer vaccines [4], and oncolytic viruses [5]. Many of those involve either the modulation of regulatory pathways associated with the immune system or involve some method of aiding antigen recognition. Oncolytic viruses infect and replicate in only cancer cells or involve some form of gene therapy through insertion of genes detrimental to cancer survival. This method involves reconstruction of the CAR receptor found on T cells to recognize specific Dig-11-ddUTP on cells that are to be destroyed. In principle and practice, this can include ex vivo growth of T cells before they are genetically modified by typically a retrotransposon introduced to the T cells by the various methods including viral vectors [6]. There are three primary components of CAR receptor including the extracellular domain, transmembrane, and intracellular domain. The primary feature of the extracellular domain is the scFv region which is similar to the light chain region of an antibody. The transmembrane domain connects the scFv region costimulatory molecules and can influence the immunogenicity depending on its length. There are four kinds of CAR T cell therapies that will be discussed. They involve the absence or presence of costimulatory molecules or the ability to stimulate cytokine production [7]. CAR T cell therapies are separated by generation as the field has progressed. Although the second generation of CAR T cell therapy has been resolved to have better cancer-killing potential than the first, there is still ambiguity on how second-generation CAR T cell therapy compared to the third or fourth generation [7]. The fourth generation is significantly different in its function of releasing cytokines and is also known as T cell redirected universal cytokine killing (TRUCK) [8].
    CAR T cell therapy
    Discussion One of the issues facing CAR T cell therapy consistency involves composition of T cells that are transduced to express various CARs. Many chemotherapies are known to induce lymphopenia in patients. This is predominantly due to the toxic nature of the chemotherapies. What is unknown is how each individual chemotherapy potentially depletes certain types of lymphocytes more so than other lymphocytes. Personal characteristics associated with the patient\'s genome and epigenome or recent exposure to a pathogen, in particular, are likely to influence the counts of various lymphocytes too. To further complicate this, patients are likely to go through different phases of chemotherapy before being introduced to immunotherapies such as CAR T cell therapy. These factors create inconsistencies in the various T cells titers. As discussed earlier, higher concentrations of transformed CD4 and CD8 CAR T cell subsets were correlated to greater killing potential [32]. As research and acceptance of immunotherapy increases amongst oncologist, there is potential for enhancing the benefits of CAR T cells by choosing to treat with immunotherapy before administration of chemotherapeutics in order to control for variability in lymphocytes. Methodology for isolating and expanding titers of specific kinds of T cells before being transduced should be implemented and examined to optimize what might be considered specific T cell dosing.