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The ability to genetically engineer oncolytic viruses in order to minimize side effects and improve the selective targeting of tumor cells has opened up novel opportunities for treating cancer. Understanding the mechanisms involved and the complex interaction between the viruses and the immune system will undoubtedly help guide the development of new strategies. Theranostic biomarkers to monitor these therapies in clinical trials serve an important need in this innovative field and demand further research.
DNA replication is a key event in the cell cycle. Although our knowledge is far from complete and many elusive regulatory mechanisms still remain beyondour grasp, many enzymes and a multiplicity of biochemical mechanisms involved have been discovered. Recent findings in E. coli have confirmed and yet surpassed the original hypothesis of F. Jacob. In yeast and higher eucaryotes, the apparent redundancy in putative origins and initiators has made an estimation of the importance of each identified element difficult to access. In spite of well established methodologies - which are also described in the book - the origin identification in mammalian chromosomes is still a controversial subject. On the other hand, considerable advances have been made in our understanding of virus DNA replication and this continues to deepen and broaden our understanding of the controls of cellular DNA replication.
Oncolytic viruses (OVs) have emerged as a promising anticancer treatment. OVs selectively infect, replicate in, and kill tumor cells. Oncolytic viral therapy occurs in two phases: an initial phase where the virus mediates direct oncolysis of tumor cells, and a second phase where an induced post-oncolytic immune response continues to mediate tumor destruction and retards progression of the disease. For a long time, the therapeutic efficacy was thought to depend mainly on the direct viral oncolysis based on their tumor selective replication and killing activities. But the post-oncolytic anti-tumor activity induced by the OV therapy is also a key factor for an efficient therapeutic activity. The topic adresses various strategies how to optimize OVs anti-tumor activity.
Chimeric antigen receptor (CAR) T cell therapies for leukemia (e.g. tisagenlecleucel) and lymphoma (e.g. axicabtagene ciloleucel) have recently received regulatory approval in the United States. Phase I/II trials have demonstrated complete remission of refractory or relapsed tumors in 50% - 94% patients. However, the clinical successes of engineered T cells for the treatment of solid malignancies have thus far been few and far between. Furthermore, several instances of severe and lethal toxicities have arisen due to on-target, off-tumor recognition of antigen by T cell products. Recent advances in phase I trials for solid tumors, as well as in pre-clinical models, have revealed several varia...