日時：	2019年3月28日 13:00~14:00
場所：	京都大学ウイルス再生研2号館（旧ウイルス研本館）1階セミナー室
演者：	Dong Sung An, MD, PhD UCLA AIDS Institute/School of Nursing
演題：	Genetic engineering of a bi-functional chimeric antigen receptor (CAR) against HIV-1 using the first heptad repeat (C46) of HIV-1 envelope glycoprotein 41.

講演要旨

A HIV cure is possible as demonstrated by the Berlin and London patients who were treated with CCR5-Δ32/Δ32 homozygous deficient bone marrow transplantations.

We have been developing anti HIV-1 gene reagents for HIV cure by a hematopoietic stem cell based gene therapy. Here, we present our development of a bi-functional chimeric antigen receptor (CAR) against HIV-1 using the membrane anchored HIV-1 fusion inhibitor, C46. C46 is a membrane-anchored HIV fusion inhibitor, derived from the C-terminal heptad repeat of HIV gp41 modified to express on cell surface. It blocks HIV-1 fusion by binding to the N-terminal coiled-coil domain of HIV gp41 fusion intermediate and prevents the six-helix bundle formation, analogous to the FDA approved soluble peptide drug enfuvirtide (T20, fuzion). Its safety has been tested in an anti HIV-1 hematopoietic stem cell based gene therapy phase I/II clinical trial (ClinicalTrials.gov Identifier: NCT01734850). We hypothesized that C46 fused with CD3ζ chain could serve as a HIV-1 specific CAR via binding the other heptad repeat in HIV-1 gp41 on the Env complex of an infected cell and mediate cytotoxic activity. C46-CAR anti-HIV-1 gene reagent should also protect C46-CAR gene modified CD4+ T cells.

I will present our resent results showing protection of lentiviral vector transduced C46-CAR gene modified T cells from HIV-1 infection as well as d CTL specificity for cytolysis HIV-1-infected target cells in vitro and reduced viral load in C46-CAR modified human hematopoietic stem/progenitor cell transplanted humanized BLT mice in vivo. Thus, this novel molecule was functional both for protecting transduced T cells from HIV-1 infection, and also in directing those T cells to have effector function against infected cells.　　　(言語：英語 　 Language: English）

主　催	京都大学ウイルス・再生医科学研究所
連絡先	システムウイルス学分野　小柳　義夫 （TEL:075-751-4813）