Author: J. Sinkovics
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  • 1 St. Joseph’s Hospital Cancer Institute Affiliated with the H. L. Moffitt Comprehensive Cancer Center at the University of South Florida College of Medicine Departments of Medical Microbiology/Immunology & Molecular Medicine Tampa FL USA
  • 2 The University of South Florida College of Medicine Tampa FL USA
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The author of the monograph “Cytolytic Immune Lymphocytes ...” (published in 2008 by Schenk Buchverlag Campus Dialog, Budapest, Passau, Pécs) proposed several research projects and described certain clinical events that require further elaboration and documentation. In this article the author provides what is required and has since become available. The first subject matter in question concerns the fusogenic viruses. The ancient fusogenic viruses might have created the first eukaryotic cell(s) by uniting archaeabacterial and prokaryotic/protobacterial protospheroplasts. Extant fusogenic viruses either produce tumor cell syncytia and lyse them, thus practicing viral oncolysis. Or, create chimaeric fusion products, the socalled “natural hybridomas”, of lymphoma cells exhibiting transmembrane budding of retrovirus particles or envelope proteins, and anti-viral specific antibody-producing plasma cells. The second topic concerns the horizontal-lateral mode of acquisition of those genes, which were “present in the waiting” in the amphioxus, sea urchin, and the agnathans, and met in the primitive gnatostomata sharks to encode in unison the entire adaptive immune system. The consensus of opinion is such that these genes derived from newly acquired transposons/retrotransposons. The author points out that the extant Epstein-Barr virus harbors genes displaying sequence homology with those genes from the sharks up to mammals that regulate the somatic hypermutation of specific antibody production. The author proposes that an ancient herpesvirus might have propagated the V(D)J and RAG genes from sea urchins to sharks. The third area is that of lymphocytes cytotoxic/cytolytic to virally infected or malignantly transformed host cells. This discovery led to the adoptive immune lymphocyte therapy of tumors. Installed in the adaptive immune system are regulatory T cells and myeloid-derived suppressor cells for he protection of “self”. Tumor cells masquerading as “self” are protected by these cells from attacks launched by immune T cells. The author supports the replacement of IL-2 by IL-15, inasmuch as IL-2 stimulates not only immune T cells, but also regulatory T cells expressing the CD25 IL-2 receptor. The administration of low dose whole body radiotherapy prior to immune lymphocyte therapy increases the efficacy of immune lymphocyte therapy. The author observed this phenomenon in the mid-1960s. The explanation of this phenomenon revealed itself just recently. In pre-irradiated hosts the intestinal wall becomes permeable to the gut flora; the intestinal bacteria activate the entire innate immune system in the mesenteric lymph nodes and a rapid activation of the adaptive immune faculties follows.

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