TumorSelect® Technology Enhancing the Safety and Efficacy of Cancer Chemotherapy

Abstract Veiled Therapeutics has developed an anticancer technology, TumorSelect® Technology, which combines proprietary anticancer prodrugs and nanotechnology, which takes advantage from current knowledge of human physiology. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Veiled’s designer prodrugs are assembled within pseudo-LDL nanoparticulates which carry them to tumor tissues where they are taken up, internalized and transformed into active drug and kill the cancer cells. This three-prong approach delivers the anticancer drug selectively to the tumors and thereby avoids or reduces the severe side effect toxicities associated with current chemotherapy. Reduction of side effect toxicity of cancer therapy by our technology will improve patient quality of life, patient retention in treatment regimes, more rapid patient recovery post treatment, and overall patient benefit.A. BackgroundThe costs of cancer, measured in terms of mortality, morbidity, direct costs of treatment, and costs of lost productivity are high.B. MethodsART-207 was synthesized; a pseudo-LDL lipid nanodispersion was formed; and mouse xenograft studies were performed. C. ResultsPreclinical toxicity, efficacy, and distribution data clearly show significant advantages of TumorSelect® paclitaxel over conventional Cremophor® formulations of paclitaxel. These advantages include:· Increased suppression of tumor growth and regrowth· Lower toxicity· Increased survival· Higher number of tumor free animals· Significantly lower concentrations of paclitaxel in non-target tissues· Significantly higher concentrations of paclitaxel in tumor tissueThus, data obtained demonstrated targeted drug delivery and support LDL-receptor dependent mechanism of selective cellular uptake by tumor tissue of TumorSelect® formulated paclitaxel.D. ConclusionsNon-target tissue concentrations of paclitaxel are significantly lower in non-tumored and tumored mice injected with formulated TumorSelect® paclitaxel compared with the mice injected with Cremophor® EL/EtOH (ethanol) paclitaxel (<20%).Tumor concentrations of paclitaxel are significantly higher in tumors of mice injected with formulated TumorSelect® paclitaxel compared with the mice injected with Cremophor® EL/EtOH paclitaxel (194%).Plasma and heart concentrations of paclitaxel are significantly lower in tumored vs. non-tumored animals injected with formulated TumorSelect® paclitaxel (<80%).Selective cellular uptake of TumorSelect® paclitaxel by tumors actively expressing LDL-receptors has been demonstrated.Tumor suppression observed was sustained for 63 days after Q1Dx5 dosing with TumorSelect® paclitaxel.TumorSelect® technology represents a potential major improvement in the clinical treatment of cancer through enhanced efficacy due to tumor-facilitated targeted delivery and reduced patient toxicity with its associated deleterious side effects.