Challenges in HIV-1 Latent Reservoir and Target Cell Quantification in CAR-T Cell and Other Lentiviral Gene Modifying HIV Cure Strategies

• 出版年: Viruses
• 主要な著者: Amanda M. Buck, Tyler-Marie Deveau, Timothy J. Henrich, Amelia N. Deitchman
• フォーマット: 論文
• 言語: 英語
• 出版事項: MDPI AG 2023-05-01
• 主題: CAR-T cells; HIV-1 cure; HIV-1 envelope expression; lentiviral vectors; gene modification; eradication
• オンライン･アクセス: https://www.mdpi.com/1999-4915/15/5/1126

Gene-modification therapies are at the forefront of HIV-1 cure strategies. Chimeric antigen receptor (CAR)-T cells pose a potential approach to target infected cells during antiretroviral therapy or following analytical treatment interruption (ATI). However, there are technical challenges in the quantification of HIV-1-infected and CAR-T cells in the setting of lentiviral CAR gene delivery and also in the identification of cells expressing target antigens. First, there is a lack of validated techniques to identify and characterize cells expressing the hypervariable HIV gp120 in both ART-suppressed and viremic individuals. Second, close sequence homology between lentiviral-based CAR-T gene modification vectors and conserved regions of HIV-1 creates quantification challenges of HIV-1 and lentiviral vector levels. Consideration needs to be taken into standardizing HIV-1 DNA/RNA assays in the setting of CAR-T cell and other lentiviral vector-based therapies to avoid these confounding interactions. Lastly, with the introduction of HIV-1 resistance genes in CAR-T cells, there is a need for assays with single-cell resolution to determine the competence of the gene inserts to prevent CAR-T cells from becoming infected in vivo. As novel therapies continue to arise in the HIV-1 cure field, resolving these challenges in CAR-T-cell therapy will be crucial.