Challenges in HIV-1 Latent Reservoir and Target Cell Quantification in CAR-T Cell and Other Lentiviral Gene Modifying HIV Cure Strategies.
Challenges in HIV-1 Latent Reservoir and Target Cell Quantification in CAR-T Cell and Other Lentiviral Gene Modifying HIV Cure Strategies.
复制标题
DOI：
10.3390/v15051126
复制
发表时间：
2023-05-09
期刊：
影响因子：
--
通讯作者：
Deitchman AN
中科院分区：
文献类型：
--
作者：
Buck AM;Deveau TM;Henrich TJ;Deitchman AN
基因修饰疗法是HIV-1治疗策略的前沿。嵌合抗原受体(CAR)-T细胞在抗逆转录病毒治疗期间或分析性治疗中断（ATI）后提供了靶向感染细胞的潜在途径。然而，在慢病毒CAR基因递送的情况下，hiv -1感染细胞和CAR- t细胞的定量以及表达靶抗原的细胞的鉴定方面存在技术挑战。首先，缺乏有效的技术来鉴定和表征在art抑制和病毒血症个体中表达高变异型HIV gp120的细胞。其次，基于慢病毒的CAR-T基因修饰载体与HIV-1保守区域之间的序列同源性给HIV-1和慢病毒载体水平的量化带来了挑战。需要考虑在CAR-T细胞和其他慢病毒载体疗法中标准化HIV-1 DNA/RNA检测，以避免这些混杂的相互作用。最后，随着CAR-T细胞中HIV-1抗性基因的引入，需要进行单细胞分辨率的检测，以确定基因插入物在体内阻止CAR-T细胞被感染的能力。随着新疗法在HIV-1治疗领域的不断出现，解决car - t细胞治疗中的这些挑战将是至关重要的。
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.
登录
查看更多内容
影响因子：
4.6
作者：
Moscoso CG;Xing L;Hui J;Hu J;Kalkhoran MB;Yenigun OM;Sun Y;Paavolainen L;Martin L;Vahlne A;Zambonelli C;Barnett SW;Srivastava IK;Cheng RH
通讯作者：
Cheng RH
影响因子：
16.6
作者：
Beckford-Vera DR;Flavell RR;Seo Y;Martinez-Ortiz E;Aslam M;Thanh C;Fehrman E;Pardons M;Kumar S;Deitchman AN;Ravanfar V;Schulte B;Wu IK;Pan T;Reeves JD;Nixon CC;Iyer NS;Torres L;Munter SE;Hyunh T;Petropoulos CJ;Hoh R;Franc BL;Gama L;Koup RA;Mascola JR;Chomont N;Deeks SG;VanBrocklin HF;Henrich TJ
通讯作者：
Henrich TJ
影响因子：
17.1
作者：
Anthony-Gonda, Kim;Bardhi, Ariola;Dropulic, Boro
通讯作者：
Dropulic, Boro
影响因子：
5.4
作者：
Ali, Ayub;Kitchen, Scott G.;Yang, Otto O.
通讯作者：
Yang, Otto O.
DOI：
10.1073/pnas.91.7.2567
发表时间：
1994-03-29
影响因子：
11.1
作者：
CHALLITA, PM;KOHN, DB
通讯作者：
KOHN, DB