Melbourne, Dec 8, 2008 AEST (ABN Newswire) - Leading developer of RNA interference (RNAi)-based therapeutics Benitec Limited (ASX:BLT)(PINK:BNIKF) announced today that Dr Amrita Krishnan, had presented a poster on the human HIV trial at the American Society of Hematology conference held in San Francisco CA USA.
Dr Krishnan is the principal clinical investigator of the pilot study being undertaken at City of Hope in Duarte, California. The presentation was entitled "First in Human Engraftment of Anti-HIV Lentiviral Vector Gene Modified CD43+ Peripheral Blood Progenitor Cells in the Treatment of AIDS Related Lymphoma (ARL)".
This pilot feasibility study is supported through a collaboration between Benitec and City of Hope and is Benitec's first human trial. The trial uses a triple therapy delivered using a lentiviral vector developed at City of Hope. The rHIV7-shl-TAR-CCR5RZ vector suppresses HIV by expressing three nucleic acids that are directed against key steps in HIV replication.
The study transplanted autologous (patient derived) blood stem cells which were genetically modified using the lentivirus vector into four AIDS patients with lymphoma who first received high doses of chemotherapy. The study showed that cells engrafted in all four patients, that new blood cells expressed the anti-HIV RNA, and there were no complications.
"We have shown that we can deliver gene modified cells which have the potential to limit the HIV infection. If we can continue to develop this approach and successfully apply it to other AIDS patients, then genetic therapy for HIV could become a reality", said Dr Krishnan.
"We are very encouraged by these initial findings. This is an extremely important trial as it is the first human clinical trial with expressed RNA interference trigger (shRNA) and the first triple gene therapy combination trial for HIV/AIDS. It is the also the first human trial for AIDS using hematopoietic stem cells (HSCs) transduced with lentiviral vectors" said Sue MacLeman, Chief Executive Officer, Benitec Limited.
The Study
The study with City of Hope is entitled, "A pilot study of the safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentiviral vector-encoding multiple anti-HIV RNA's."
The pilot study is designed to determine the safety and feasibility of RNA-based anti-HIV therapy with lentivirus-transduced hematopoietic progenitor cells (HPC) in patients undergoing autologous hematopoietic stem cell transplantation (HCT) for intermediate and high grade AIDS lymphoma.
The lentivirus vector encodes three forms of anti-HIV RNA: RNAi in the form of a short hairpin RNA (shRNA) targeted to an exon in HIV-1 tat/rev (shI), a decoy for the HIV TAT-reactive element (TAR), and a ribozyme that targets the host cell CCR5 chemokine receptor (CCR5RZ). The vector, used to transduce autologous CD34-selected HPC, is called rHIV7-shI-TAR-CCR5RZ and was manufactured by the Center for Biomedicine and Genetics at City of Hope.
Following standard mobilization of HPC and collection by apheresis (HPC-A), a portion of the cells were cryo-preserved and left unmanipulated for later use as treatment. The remaining portions of the cells were enriched for CD34+ cells, cryo-preserved, and later genetically modified by infection with rHIV7-shI-TAR-CCR5RZ.
The subjects underwent conditioning therapy and at the time of autologous HCT, the rHIV7-shI-TAR-CCR5RZ transduced cells were infused, followed 24-hrs later by the infusion of untransduced autologous HPC-A.
About City of Hope
City of Hope is a leading research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a Comprehensive Cancer Center, the highest honor bestowed by the National Cancer Institute, and a founding member of the National Comprehensive Cancer Network, City of Hope's research and treatment protocols advance care throughout the nation. City of Hope is located in Duarte, Calif., just northeast of Los Angeles, and is ranked as one of "America's Best Hospitals" in cancer and urology by U.S.News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics. For more information, visit www.cityofhope.org.
Contact
Sue MacLeman
Chief Executive Officer
TEL: +61-437-211-200
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