Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities

References

• Weiss RA. How does HIV cause AIDS? Science. 1993;260:1273–1279. doi: 10.1126/science.8493571
   PubMed Web of Science ®Google Scholar
• Wada N, Jacobson LP, Cohen M, et al. Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed simultaneously in long-term cohort studies, 1984-2008. Am J Epidemiol 2013;177(2):116–125. doi:10.1093/aje/kws321.
   PubMed Web of Science ®Google Scholar
• Mugo NR, Ngure K, Kiragu M, et al. The pre-exposure prophylaxis revolution; from clinical trials to programmatic implementation. Curr Opin HIV AIDS. 2016;11:80–86. doi:10.1097/COH.0000000000000224.
   PubMed Web of Science ®Google Scholar
• Sultan B, Benn P, Waters L. Current perspectives in HIV post-exposure prophylaxis. HIV AIDS (Auckl). 2014;6:147–158. doi:10.2147/HIV.S46585.
   PubMedGoogle Scholar
• Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278:1295–1300. doi: 10.1126/science.278.5341.1295
   PubMed Web of Science ®Google Scholar
• Ledgerwood JE, Coates EE, Yamshchikov G, et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015;182:289–301. doi:10.1111/cei.12692.
   PubMed Web of Science ®Google Scholar
• Schoofs T, Klein F, Braunschweig M, et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016;352:997–1001. doi:10.1126/science.aaf0972.
   PubMed Web of Science ®Google Scholar
• Igarashi T, Brown C, Azadegan A, et al. Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma. Nat Med. 1999;5:211–216. doi: 10.1038/5576
   PubMed Web of Science ®Google Scholar
• Lu CL, Murakowski DK, Bournazos S, et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science. 2016;352:1001–1004. doi:10.1126/science.aaf1279.
   PubMed Web of Science ®Google Scholar
• Malbec M, Porrot F, Rua R, et al. Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission. J Exp Med. 2013;210:2813–2821. doi:10.1084/jem.20131244.
   PubMed Web of Science ®Google Scholar
• Ackerman ME, Barouch DH, Alter G. Systems serology for evaluation of HIV vaccine trials. Immunol Rev. 2017;275:262–270. doi: 10.1111/imr.12503
   PubMed Web of Science ®Google Scholar
• Gama L, Koup RA. New-generation high-potency and designer antibodies: Role in HIV-1 treatment. Annu Rev Med. 2018;69:409–419. doi:10.1146/annurev-med-061016-041032.
   PubMed Web of Science ®Google Scholar
• Gorny MK, Xu JY, Karwowska S, et al. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol. 1993;150:635–643.
   PubMed Web of Science ®Google Scholar
• Thali M, Moore JP, Furman C, et al. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J Virol. 1993;67:3978–3988. doi: 10.1128/JVI.67.7.3978-3988.1993
   PubMed Web of Science ®Google Scholar
• Zwick MB, Labrijn AF, Wang M, et al. Broadly neutralizing antibodies targeted to the membrane proximal external region. J Virol. 2001;75:10892–10905. doi: 10.1128/JVI.75.22.10892-10905.2001
   PubMed Web of Science ®Google Scholar
• Jr WA, Scharf L, Horwitz J, et al. Computational analysis of anti-HIV-1 antibody neutralization panel data to identify potential functional epitope residues. Proc Natl Acad Sci U S A. 2013;110:10598–10603. doi:10.1073/pnas.1309215110.
   PubMed Web of Science ®Google Scholar
• Trkola A, Kuster H, Rusert P, et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med. 2005;11:615–622. doi: 10.1038/nm1244
   PubMed Web of Science ®Google Scholar
• Mehandru S, Vcelar B, Wrin T, et al. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J Virol. 2007;81:11016–11031. doi: 10.1128/JVI.01340-07
   PubMed Web of Science ®Google Scholar
• Haynes BF, Fleming J, St Clair EW, et al. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science. 2005;308:1906–1908. doi: 10.1126/science.1111781
   PubMed Web of Science ®Google Scholar
• Yang G, Holl TM, Liu Y, et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J Exp Med. 2013;210:241–256. doi:10.1084/jem.20121977.
   PubMed Web of Science ®Google Scholar
• Sok D, Burton DR. Recent progress in broadly neutralizing antibodies to HIV. Nat Immunol. 2018;19:1179–1188. doi:10.1038/s41590-018-0235-7.
   PubMed Web of Science ®Google Scholar
• Moldt B, Rakasz EG, Schultz N, et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci U S A. 2012;109:18921–18925. doi:10.1073/pnas.1214785109.
   PubMed Web of Science ®Google Scholar
• Gautam R, Nishimura Y, Pegu A, et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature. 2016;533:105–109. doi:10.1038/nature17677.
   PubMed Web of Science ®Google Scholar
• Barouch DH, Whitney JB, Moldt B, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013;503:224–228. doi:10.1038/nature12744.
   PubMed Web of Science ®Google Scholar
• Cunningham CK, McFarland EJ, Morrison RL, et al. Safety, tolerability, and pharmacokinetics of the broadly neutralizing HIV-1 monoclonal antibody VRC01 in HIV-exposed Newborn infants. J Infect Dis. 2019: jiz532. doi:10.1093/infdis/jiz532.
   Web of Science ®Google Scholar
• Mayer KH, Seaton KE, Huang Y, et al. Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: results of a phase 1 randomized trial. PLoS Med 2017;14:e1002435. doi:10.1371/journal.pmed.1002435.
   PubMed Web of Science ®Google Scholar
• Lynch RM, Boritz E, Coates EE, et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015;7:319ra206. doi:10.1126/scitranslmed.aad5752.
   PubMed Web of Science ®Google Scholar
• Bar KJ, Sneller MC, Harrison LJ, et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med. 2016;375:2037–2050. doi: 10.1056/NEJMoa1608243
   PubMed Web of Science ®Google Scholar
• Crowell TA, Colby DJ, Pinyakorn S, et al. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet HIV. 2019;6(5):e297–e306. doi:10.1016/S2352-3018(19)30053-0.
   PubMed Web of Science ®Google Scholar
• Caskey M, Klein F, Lorenzi JC, et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015;522:487–491. doi:10.1038/nature14411.
   PubMed Web of Science ®Google Scholar
• Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535:556–560. doi: 10.1038/nature18929
   PubMed Web of Science ®Google Scholar
• Caskey M, Schoofs T, Gruell H, et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat Med. 2017;23:185–191. doi:10.1038/nm.4268.
   PubMed Web of Science ®Google Scholar
• Mendoza P, Gruell H, Nogueira L, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018;561:479–484. doi:10.1038/s41586-018-0531-2.
   PubMed Web of Science ®Google Scholar
• Bar-On Y, Gruell H, Schoofs T, et al. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med. 2018;24:1701–1707. doi:10.1038/s41591-018-0186-4.
   PubMed Web of Science ®Google Scholar
• Stephenson KE, Julg B, Ansel J, et al. Conference on Retroviruses and Opportunistic Infections; 2019, March 4-7; Seattle, USA.
   Google Scholar
• Gaudinski MR, Coates EE, Houser KV, et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018;15:e1002493. doi:10.1371/journal.pmed.1002493.
   PubMed Web of Science ®Google Scholar
• Gaudinski MR, Houser KV, Doria-Rose NA, et al. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV. 2019;6:e667–e679. doi:10.1016/S2352-3018(19)30181-X.
   PubMed Web of Science ®Google Scholar
• Glassman PM, Balthasar JP. Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med. 2014;11:20–33. doi:10.7497/j.issn.2095-3941.
   PubMedGoogle Scholar
• Jolly C, Kashefi K, Hollinshead M, et al. HIV-1 cell to cell transfer across an Envinduced, actin-dependent synapse. J Exp Med. 2004;199:283–293. doi: 10.1084/jem.20030648
   PubMed Web of Science ®Google Scholar
• Alvarez RA, Barria MI, Chen BK. Unique features of HIV-1 spread through T cell virological synapses. PLoS Pathog. 2014;10:e1004513. doi:10.1371/journal.ppat.1004513.
   PubMed Web of Science ®Google Scholar
• Sourisseau M, Sol-Foulon N, Porrot F, et al. Inefficient human immunodeficiency virus replication in mobile lymphocytes. J Virol. 2007;81:1000–1012. doi: 10.1128/JVI.01629-06
   PubMed Web of Science ®Google Scholar
• Mazurov D, Ilinskaya A, Heidecker G, et al. Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors. PLoS Pathog. 2010;26(6):e1000788. doi:10.1371/journal.ppat.1000788.
   Web of Science ®Google Scholar
• Sattentau QJ. The direct passage of animal viruses between cells. Curr Opin Virol. 2011;1:396–402. doi:10.1016/j.coviro.2011.09.004.
   PubMed Web of Science ®Google Scholar
• Dale BM, Alvarez RA, Chen BK. Mechanisms of enhanced HIV spread through T-cell virological synapses. Immunol Rev. 2013;251:113–124. doi:10.1111/imr.12022.
   PubMed Web of Science ®Google Scholar
• Del Portillo A, Tripodi J, Najfeld V, et al. Multiploid inheritance of HIV-1 during cell-to-cell infection. J Virol. 2011;85:7169–7176. doi:10.1128/JVI.00231-11.
   PubMed Web of Science ®Google Scholar
• Chazal M, Nzounza P, Pique C, et al. Loss of infectivity of HIV-1 particles produced by mobile lymphocytes. PLoS One. 2014;9:e109601. doi:10.1371/journal.pone.0109601.
   PubMed Web of Science ®Google Scholar
• Chen P, Hübner W, Spinelli MA, et al. Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses. J Virol. 2007;81:12582–12595. doi: 10.1128/JVI.00381-07
   PubMed Web of Science ®Google Scholar
• Sigal A, Kim JT, Balazs AB, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature. 2011;477:95–98. doi:10.1038/nature10347.
   PubMed Web of Science ®Google Scholar
• Abela IA, Berlinger L, Schanz M, et al. Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies. PLoS Pathog. 2012;8:e1002634. doi:10.1371/journal.ppat.1002634.
   PubMed Web of Science ®Google Scholar
• Ganesh L, Leung K, Lore K, et al. Infection of specific dendritic cells by CCR5-tropic human immunodeficiency virus type 1 promotes cell-mediated transmission of virus resistant to broadly neutralizing antibodies. J Virol. 2004;78:11980–11987. doi: 10.1128/JVI.78.21.11980-11987.2004
   PubMed Web of Science ®Google Scholar
• Massanella M, Puigdomenech I, Cabrera C, et al. Antigp41 antibodies fail to block early events of virological synapses but inhibit HIV spread between T cells. AIDS. 2009;23:183–188. doi:10.1097/QAD.0b013e32831ef1a3.
   PubMed Web of Science ®Google Scholar
• Martin N, Welsch S, Jolly C, et al. Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. J Virol. 2010;84:3516–3527. doi:10.1128/JVI.02651-09.
   PubMed Web of Science ®Google Scholar
• Reh L, Magnus C, Schanz M, et al. Capacity of broadly neutralizing antibodies to inhibit HIV-1 cell-cell transmission Is Strain- and epitope-dependent. PLoS Pathog. 2015;11:e1004966. doi:10.1371/journal.ppat.1004966.
   PubMed Web of Science ®Google Scholar
• Li H, Zony C, Chen P, et al. Reduced potency and Incomplete neutralization of broadly neutralizing antibodies against cell-to-cell transmission of HIV-1 with Transmitted Founder Envs. J Virol. 2017;91(9):pii: e02425-16. doi:10.1128/JVI.02425-16.
   Web of Science ®Google Scholar
• Parsons MS, Lloyd SB, Lee WS, et al. Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection. Sci Transl Med. 2017;9(402):pii: eaaf1483. doi:10.1126/scitranslmed.aaf1483.
   Web of Science ®Google Scholar
• Chun TW, Engel D, Berrey MM, et al. Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A. 1998;95:8869–8873. doi: 10.1073/pnas.95.15.8869
   PubMed Web of Science ®Google Scholar
• Bournazos S, DiLillo DJ, Ravetch JV. The role of Fc-FcγR interactions in IgG-mediated microbial neutralization. J Exp Med. 2015;212:1361–1369. doi:10.1084/jem.20151267.
   PubMed Web of Science ®Google Scholar
• Diskin R, Scheid JF, Marcovecchio PM, et al. Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science. 2011;334:1289–1293. doi:10.1126/science.1213782.
   PubMed Web of Science ®Google Scholar
• Rujas E, Leaman DP, Insausti S, et al. Functional optimization of broadly neutralizing HIV-1 antibody 10E8 by Promotion of membrane interactions. J Virol. 2018;92(8):pii: e02249-17. doi:10.1128/JVI.02249-17.
   Web of Science ®Google Scholar
• Liu Q, Lai YT, Zhang P, et al. Improvement of antibody functionality by structure-guided paratope engraftment. Nat Commun. 2019;10:721. doi:10.1038/s41467-019-08658-4.
   PubMed Web of Science ®Google Scholar
• Song R, Oren DA, Franco D, et al. Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity. Nat Biotechnol. 2013;31:1047–1052. doi:10.1038/nbt.2677.
   PubMed Web of Science ®Google Scholar
• Ward ES, Ober RJ. Chapter 4: Multitasking by exploitation of intracellular transport functions the many faces of FcRn. Adv Immunol. 2009;103:77–115. doi:10.1016/S0065-2776(09)03004-1.
   PubMed Web of Science ®Google Scholar
• Ko SY, Pegu A, Rudicell RS, et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature. 2014;514:642–645. doi:10.1038/nature13612.
   PubMed Web of Science ®Google Scholar
• Gautam R, Nishimura Y, Gaughan N, et al. A single injection of crystallizable fragment domain modifed antibodies elicits durable protection from SHIV infection. Nat Med. 2018;24:610–616. doi:10.1038/s41591-018-0001-2.
   PubMed Web of Science ®Google Scholar
• Johnson PR, Schnepp BC, Zhang J, et al. Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys. Nat Med. 2009;15:901–906. doi:10.1038/nm.1967.
   PubMed Web of Science ®Google Scholar
• Saunders KO, Wang L, Joyce MG, et al. Broadly neutralizing human immunodeficiency virus type 1 antibody gene transfer protects nonhuman primates from mucosal Simian-human immunodeficiency virus infection. J Virol. 2015;89:8334–8345. doi:10.1128/JVI.00908-15.
   PubMed Web of Science ®Google Scholar
• Balazs AB, Chen J, Hong CM, et al. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature. 2011;481:81–84. doi:10.1038/nature10660.
   PubMed Web of Science ®Google Scholar
• Badamchi-Zadeh A, Tartaglia LJ, Abbink P, et al. Therapeutic efficacy of Vectored PGT121 gene Delivery in HIV-1-infected humanized mice. J Virol. 2018;92:e01925–17. doi:10.1128/JVI.01925-17.
   PubMed Web of Science ®Google Scholar
• Priddy FH, Lewis DJM, Gelderblom HC, et al. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial. Lancet HIV. 2019;6:e230–e239. doi:10.1016/S2352-3018(19)30003-7.
   PubMed Web of Science ®Google Scholar
• Klein F, Halper-Stromberg A, Horwitz JA, et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature. 2012;492:118–122. doi:10.1038/nature11604.
   PubMed Web of Science ®Google Scholar
• Julg B, Liu PT, Wagh K, et al. Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail. Sci Transl Med. 2017;9(408). doi:10.1126/scitranslmed.aao4235.
   Web of Science ®Google Scholar
• Asokan M, Rudicell RS, Louder M, et al. Bispecifc antibodies targeting diferent epitopes on the HIV-1 envelope exhibit broad and potent neutralization. J Virol. 2015;89:12501–12512. doi:10.1128/JVI.02097-15.
   PubMed Web of Science ®Google Scholar
• Wagh K, Seaman MS, Zingg M, et al. Potential of conventional & bispecifc broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections. PLoS Pathog. 2018;14:e1006860. doi:10.1371/journal.ppat.1006860.
   PubMed Web of Science ®Google Scholar
• Xu L, Pegu A, Rao E, et al. Trispecifc broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science. 2017;358:85–90. doi:10.1126/science.aan8630.
   PubMed Web of Science ®Google Scholar
• Steinhardt JJ, Guenaga J, Turner HL, et al. Rational design of a trispecifc antibody targeting the HIV-1 Env with elevated anti-viral activity. Nat Commun. 2018;9:877. doi:10.1038/s41467-018-03335-4.
   PubMed Web of Science ®Google Scholar
• Duncan CJ, Williams JP, Schiffner T, et al. High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse. J Virol. 2014;88:2025–2034. doi:10.1128/JVI.03245-13.
   PubMed Web of Science ®Google Scholar
• McCoy LE, Groppelli E, Blanchetot C, et al. Neutralisation of HIV-1 cell-cell spread by human and llama antibodies. Retrovirology. 2014;11:83. doi:10.1186/s12977-014-0083-y.
   PubMed Web of Science ®Google Scholar
• Wang CY, Wong WW, Tsai HC, et al. Effect of anti-CD4 antibody UB-421 on HIV-1 rebound after treatment interruption. N Engl J Med. 2019;380:1535–1545. doi:10.1056/NEJMoa1802264.
   PubMed Web of Science ®Google Scholar
• Emu B, Fessel J, Schrader S, et al. Phase 3 study of ibalizumab for Multidrug-resistant HIV-1. N Engl J Med. 2018;379:645–654. doi:10.1056/NEJMoa1711460.
   PubMed Web of Science ®Google Scholar
• A Randomized, Double-blind, Placebo-controlled Trial, Followed by Single-arm Treatment of PRO 140 in Combination w/Optimized Background Therapy in Treatment-Experienced HIV Subjects. (PRO 140). ClinicalTrials. gov. U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT02483078?term=PRO140&rank=2.8
   Google Scholar
• Buzon MJ, Martin-Gayo E, Pereyra F, et al. Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J Virol. 2014;88:10056–10065. doi:10.1128/JVI.01046-14.
   PubMed Web of Science ®Google Scholar
• Hessell AJ, Jaworski JP, Epson E, et al. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nat Med. 2016;22:362–368. doi:10.1038/nm.4063.
   PubMed Web of Science ®Google Scholar
• Nishimura Y, Gautam R, Chun TW, et al. Early antibody therapy can induce long-lasting immunity to SHIV. Nature. 2017;543:559–563. doi:10.1038/nature21435.
   PubMed Web of Science ®Google Scholar
• Halper-Stromberg A, Lu CL, Klein F, et al. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell. 2014;158:989–999. doi:10.1016/j.cell.2014.07.043.
   PubMed Web of Science ®Google Scholar
• Borducchi EN, Liu J, Nkolola JP, et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature. 2018;563:360–364. doi:10.1038/s41586-018-0600-6.
   PubMed Web of Science ®Google Scholar
• Liu B, Zou F, Lu L, et al. Chimeric antigen receptor T cells Guided by the single-chain Fv of a broadly neutralizing antibody Specifically and effectively Eradicate virus reactivated from latency in CD4+ T Lymphocytes isolated from HIV-1-infected individuals receiving Suppressive combined antiretroviral therapy. J Virol. 2016;90:9712–9724. doi:10.1128/JVI.00852-16.
   PubMed Web of Science ®Google Scholar
• Anthony-Gonda K, Bardhi A, Ray A, et al. Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Sci Transl Med. 2019;11:eaav5685. doi: 10.1126/scitranslmed.aav5685
   PubMed Web of Science ®Google Scholar
• Herzig E, Kim KC, Packard TA, et al. Attacking latent HIV with convertibleCAR-T cells, a highly adaptable killing platform. Cell. 2019;179:880–894. doi:10.1016/j.cell.2019.10.002.
   PubMed Web of Science ®Google Scholar