Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients.

Recombinant adeno-associated viruses as a gene delivery vehicle for the use in molecular medicine

Breast cancer (BC) is a cancer with a high prevalence and mortality among women worldwide. With the current diagnostics methods, BC may remain undetected at its early stages, and the therapies developed for the disease are associated with severe side effects. Oncolytic viruses can be the basis of the new, effective BC treatment approaches. The viruses destroy tumor cells directly and launch the antitumor immune response; this dual action supports their efficacy. It is possible to make the oncolytic virus therapy more effective by designing genetically modified viruses that can target BC cells better and/or induce a stronger antitumor immune response. This review outlines the directions of development of oncolytic viruses in BC treatment, covers the optimal ways of delivering viruses to the tumor and the efficacy of their use in combination with other therapeutic agents (methods) and presents the prospects of using oncolytic viruses in antitumor vaccines.

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap is substantial enough that breakthroughs in one therapeutic could have considerable implications on the progression of the other two. Each oncotherapeutic modality has accomplished clinical translation, successfully overcoming the potential pitfalls promising therapeutics face. However, once studies enter clinical trials, the data all but disappears, leaving pre-clinical researchers largely in the dark. Overall, the creativity, flexibility, and innovation of these modalities for solid tumor treatments are greatly encouraging, and usher in a new age of pharmaceutical development.

EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL

The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.