Periodic Reporting for period 1 - Cancer-Targeted PolyIC (Treatment of EGFR over-expressing cancers by targeted non-viral delivery of PolyIC)
Okres sprawozdawczy: 2015-02-01 do 2016-07-31
We have recently developed a technology that enables targeted delivery of double-stranded RNA, Poly Inosine/Poly Cytosine (PolyIC), into EGFR overexpressing cancers. EGFR is overexpressed in many cancers and therefore has been a target for many drugs.
We have shown that application of epidermal growth factor receptor (EGFR)-targeted synthetic dsRNA, Poly Inosine/Poly Cytosine (PolyIC), is highly efficient and selective against deadly cancers overexpressing EGFR, including glioblastoma , breast cancer and adenocarcinoma. Double-stranded RNA, frequently expressed in cells infected by viruses, activates a number of pro-apoptotic and pro-inflammatory processes simultaneously. These dsRNA-induced mechanisms efficiently kill infected cells and induce expression of anti-proliferative cytokines from the interferon (IFN) family, which prevent further spread of the virus.
During this grant period we have continued the development of EGFR targeting conjugates, in our aim to reach the clinic. Based on our studies we decided to pursue the development of one of the conjugates, PP-EGFRAffibody.
We were able to produce it in large scale for in vitro and in vivo studies and to analyze the conjugate for its biophysical characteristics. We have demonstrated that the conjugate is highly effective in vitro in cell killing. Several in vivo studies were conducted in order to analyze toxicity, maximal dosage and efficacy. Our studies revealed that the conjugate is highly effective in inhibiting adenocarcinoma tumor growth in vivo with no toxicity. Our in vitro studies demonstrated that targeted delivery of polyIC using PP-EGFRAffibody induced a profound immune response and resulted in immune cell recruitment. We were further able to show that the targeted delivery of poly IC induces activation of immune cells and a profound bystander effect.
In the business aspect, we prepared a business plan and executive summary. During this period we met with several different investors in an aim to commercialize the compound. We are currently waiting to hear back from potential investors.
We have shown that application of epidermal growth factor receptor (EGFR)-targeted synthetic dsRNA, Poly Inosine/Poly Cytosine (PolyIC), is highly efficient and selective against deadly cancers overexpressing EGFR, including glioblastoma , breast cancer and adenocarcinoma. Double-stranded RNA, frequently expressed in cells infected by viruses, activates a number of pro-apoptotic and pro-inflammatory processes simultaneously. These dsRNA-induced mechanisms efficiently kill infected cells and induce expression of anti-proliferative cytokines from the interferon (IFN) family, which prevent further spread of the virus.
During this grant period we have continued the development of EGFR targeting conjugates, in our aim to reach the clinic. Based on our studies we decided to pursue the development of one of the conjugates, PP-EGFRAffibody.
We were able to produce it in large scale for in vitro and in vivo studies and to analyze the conjugate for its biophysical characteristics. We have demonstrated that the conjugate is highly effective in vitro in cell killing. Several in vivo studies were conducted in order to analyze toxicity, maximal dosage and efficacy. Our studies revealed that the conjugate is highly effective in inhibiting adenocarcinoma tumor growth in vivo with no toxicity. Our in vitro studies demonstrated that targeted delivery of polyIC using PP-EGFRAffibody induced a profound immune response and resulted in immune cell recruitment. We were further able to show that the targeted delivery of poly IC induces activation of immune cells and a profound bystander effect.
In the business aspect, we prepared a business plan and executive summary. During this period we met with several different investors in an aim to commercialize the compound. We are currently waiting to hear back from potential investors.