- |||||||||| PGT121 / Gilead, IAVI, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Semen enhances transmitted/founder HIV-1 infection and only marginally reduces antiviral activity of broadly neutralizing antibodies. (Pubmed Central) - Mar 19, 2024
Understanding this interaction is crucial for developing better strategies to prevent HIV-1 transmission. By incorporating the knowledge gained from this study, scientists can now focus on creating microbicides that consider the impact of semen, bringing us closer to more effective prevention methods.
- |||||||||| Intron A (interferon ?-2b) / Merck (MSD), Biogen, 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Autologous Neutralizing Antibodies Contribute to Virus Control in a Subset of PWH Treated With bNAbs () - Mar 16, 2024 - Abstract #CROI2024CROI_1197;
P1
To determine the relative selective pressure of bnAbs and anAbs in the BEAT2 study of 3BNC117, 10-1074, and IFNa2b, we performed a sieve analysis comparing the potency of administered bnAbs and host anAbs against reservoir and rebound Envs.In 8 participants of BEAT2 (NCT03588715), we sequenced provirus from PBMCs collected at study enrollment via FLIPseq or MIPseq (n= 314) to identify intact HIV-1 genomes in single and clonally-expanded populations...In the BEAT2 study of 2 bnAbs and IFNa2b, the greater potency of the administered bnAbs against reservoir vs. rebound Envs indicates bnAb selective pressure. In 2 participants with delayed rebound, baseline anAbs also exerted selective pressure.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Broadly Neutralizing Antibody-Secreting T Cells and CAR-Ts Potently Suppress In Vivo HIV Infection () - Mar 16, 2024 - Abstract #CROI2024CROI_1195;
BNAb-secreting T cells synergized with CAR-T cells to potently suppress in vivo HIV infection. This combinational therapy incorporating cellular and humoral anti-HIV approach provides a new strategy to generate more potent immunotherapeutics to contribute to a functional cure of HIV infection.
- |||||||||| Long Half-Life Broadly Neutralizing Killer Bispecifics Against HIV-1: Harnessing the Immune System (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_1087;
Our data highlights the design and characterization of novel DNA launched immunotherapeutic against HIV-1, which possess significant characteristics of a promising immunotherapy having broad neutralization capacities of a Tier 2/3 global virus panel, specific engagement of effector cells and killing of the infected target cells and longer serum half-life in comparison to conventional bispecific T cell engaging molecules. Delivery of LHL-BnKs as combination therapy
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Lower ADCC After 26 Weeks of PEG-IFN-?2b and 2 bNAbs in Otherwise Suppressed HIV-1+ (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_258;
P1
Background: Previous studies suggested that pegylated interferon ?2b (peg-IFN-?2b) and the broadly neutralizing antibodies (bNabs) 3BNC117 and 10-1074 may contribute to cure-related strategies. In PWH, combined immunotherapy with peg-IFN-?2b+bNAbs resulted in no effect on IFN-?-induced NK direct cytotoxicity and an unexpected decrease in gp120-induced ADCC and in circulating CD16+ NK cell subsets.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Slope of Neutralization Curve is Best Predictor of Viral Decay Response to 3BNC117 at ART Initiation (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_257;
Whilst bNAb sensitivity is crucial for clinical outcome in clinical trials administering bNAbs, so far bNAb sensitivity threshold has been based on expert opinions. Using clinical data from the eCLEAR trial, we have shown that the best predictors of bNAb-mediated effects on plasma HIV-1 RNA decay are the slope of the neutralization curve from the PhenoSense assay.
- |||||||||| PGT121 / Gilead, IAVI, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Variable HIV-1 C Env Characteristics Associated With Predicted bNAb Resistance in Botswana (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_190;
V1 charge distributions were significantly different for VRC26.25 (p =0.01), PGT121(p <0.01) and VRC01 (p = 0.01) resistant strains...We observe the mutation T234N in sequences resistant to 3BNC117 and b12. Our findings further highlight the need to evaluate VC from sequence data, to determine the optimal vaccine design and best bnAb combinations to use for neutralization of highly variable HIV-1 subtype C.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, PGDM1400 / National Institute of Allergy and Infectious Diseases, IAVI
An Efficient Envelope Genotypic Assay to Identify bNAb Susceptibility in Infants with HIV (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_183;
Applying our workflow, the predicted susceptibility to bNAbs varied across individuals due to high levels of inter-patient Env diversity. Early ART-treated infants often have viraemia due to adherence challenges.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Immune Responses and HIV Reservoir Evolution From Pre-ART to 5 Years Into Post-Treatment Control () - Mar 5, 2024 - Abstract #CROI2024CROI_146;
Background: In the randomized-controlled eCLEAR study focusing on the administration of the broadly neutralizing antibody 3BNC117 at the time of ART initiation, one post-treatment controller was identified...Post-treatment control in this individual was associated with persistence of genome-intact HIV-1 proviruses that grew out under in vitro tissue culture assays but not under physiological in vivo conditions. This is possibly due to a strong immune-mediated selection of intact proviruses in heterochromatin locations that may have a weaker ability to drive rebound in vivo.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Broadly neutralizing antibody epitopes on HIV-1 particles are exposed after virus interaction with host cells. (Pubmed Central) - Oct 4, 2023
Our data suggest that antibody epitopes including V2q (e.g., PG9, PGT145), CD4bs (e.g., VRC01, 3BNC117), and V3 (2219, 2557) are masked on HIV-1 particles...These data provide insight on how bNAbs may gain access to these occluded epitopes to exert their neutralization effects and block HIV-1 infection. These findings have important implications for the way we evaluate the neutralizing efficacy of antibodies and can potentially guide vaccine design.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Trial completion: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - May 23, 2023
P2a, N=47, Completed,
Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses. Active, not recruiting --> Completed
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, teropavimab (GS-5423) / Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Evaluation of therapeutic concentrations of anti-HIV antibodies 3BNC117/teropavimab and 10-1074/zinlirvirmab through PK-PD modeling and prediction of the washout duration in HIV cure studies (Poster Exhibition area) - May 5, 2023 - Abstract #IASHIV2023IAS_HIV_467;
Active, not recruiting --> Completed Embargoes on oral abstracts and posters lift on Monday, 24 July 2023, at 09:00 Australian Eastern Standard Time (AEST).
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Vaccinal effect of HIV-1 antibody therapy: dream or reality? (Pubmed Central) - May 5, 2023
HIV-1 bNAbs can enhance adaptive host immune responses in PLWH. The challenge now is to exploit these immunomodulatory properties to design optimized therapeutic interventions to promote and enhance the induction of protective immunity against HIV-1 infection during bNAbs therapy.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
THE IMPACT OF 3BNC117; 10-1074; AND LEFITOLIMOD ON HIV-1 PERSISTENCE: THE TITAN TRIAL (Ballroom 1 (Level 5)) - Feb 13, 2023 - Abstract #CROI2023CROI_211;
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Preclinical, Journal, CAR T-Cell Therapy, PD(L)-1 Biomarker, IO biomarker: Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance specific cytotoxic activity against HIV Env cells in vivo. (Pubmed Central) - Jan 20, 2023
Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 (3BE) CAR construct that enabled the expression of programmed cell death protein (PD-1) -blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV Env...Furthermore, we manufactured TCR-deficient 3BE CAR-T cells through gene editing and demonstrated that these CAR-T cells could effectively kill HIV Env cells in vivo without the occurrence of severe graft-versus-host disease (GvHD) in NSG mice. These data suggest that we have provided a feasible approach to the generation of "off-the-shelf" anti-HIV CAR-T cells in combination with PD-1 checkpoint blockade immunotherapy, which can be a powerful therapeutic candidate for the functional cure of HIV.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, Istodax (romidepsin) / Astellas, BMS
P1/2 data, Journal: Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. (Pubmed Central) - Nov 22, 2022
P2
We conclude that 3BNC117 at ART initiation enhanced elimination of plasma viruses and infected cells, enhanced HIV-1-specific CD8 immunity and was associated with sustained ART-free virologic control among persons with 3BNC117-sensitive virus. These findings strongly support interventions administered at the time of ART initiation as a strategy to limit long-term HIV-1 persistence.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8 T cell immunity. (Pubmed Central) - Nov 6, 2022
To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment...Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8 T cell responses that are associated with ART-free virologic control.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Preclinical, Journal: In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice. (Pubmed Central) - Aug 17, 2022
Here we report in vivo B cell engineering using two adeno-associated viral vectors, with one coding for Staphylococcus aureus Cas9 (saCas9) and the other for 3BNC117, an anti-HIV bNAb...We observed minimal clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 off-target cleavage as detected by unbiased CHANGE-sequencing analysis, whereas on-target cleavage in undesired tissues is reduced by expressing saCas9 from a B cell-specific promoter. In vivo B cell engineering to express therapeutic antibodies is a safe, potent and scalable method, which may be applicable not only to infectious diseases but also in the treatment of noncommunicable conditions, such as cancer and autoimmune disease.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Enrollment change: Romidepsin Plus 3BNC117 Phase 2a Study (clinicaltrials.gov) - Jul 14, 2022
P2a, N=48, Completed,
In vivo B cell engineering to express therapeutic antibodies is a safe, potent and scalable method, which may be applicable not only to infectious diseases but also in the treatment of noncommunicable conditions, such as cancer and autoimmune disease. N=21 --> 48
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Clinical, Journal: Combination anti-HIV antibodies provide sustained virological suppression. (Pubmed Central) - Jun 11, 2022
Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention. (Pubmed Central) - May 12, 2022
In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.
- |||||||||| VRC01 / Acuitas Therap
Identification of viral mutations that confer cross resistance to VRC01 antibody in HIV-1 subtype C viruses () - May 12, 2022 - Abstract #AIDS2022AIDS_1155;
Overall, our data supports the concept that some HIV-1 subtype C isolates change critical CD4 binding features to escape VRC01, some causing cross-resistance to other CD4 binding antibodies. The data also promote continued efforts of characterizing VRC01 resistant sites in preparation for future passive immunity trials that include CD4bs antibodies.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
AAV-mediated Delivery of Anti-HIV Antibodies to the CNS (Room 204) - May 6, 2022 - Abstract #ASGCT2022ASGCT_1812;
While the ADA problem was not solved in our experimental conditions, our data show AAV-delivered antibodies were detectable in CSF with the delivery method used. Eradicating or minimizing ADA responses is crucial to make the AAV-delivery of antibodies a consistent and reliable approach against HIV.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Three Examples of Long-term AIDS Virus Suppression Using AAV-delivered Monoclonal Antibodies (Room 204) - May 6, 2022 - Abstract #ASGCT2022ASGCT_1811;
Here we report that monkey rh2438 continues to be suppressed for over 6 years and continues to express high levels of antibodies 10-1074 and 3BNC117 in serum (approx. Our data show that durable, continuous antibody expression can be achieved with AAV (in the absence of strong ADA responses) and support the potential for lifelong suppression of viral loads with the AAV-antibody approach.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, lefitolimod (MGN1703) / OncXerna Therap, iPharma, Gilead
Enrollment closed: TITAN: Combining TLR9 Agonist With bNAbs for Reservoir Reduction and Immunological Control of HIV (clinicaltrials.gov) - Mar 31, 2022
P2a, N=47, Active, not recruiting,
Our data show that durable, continuous antibody expression can be achieved with AAV (in the absence of strong ADA responses) and support the potential for lifelong suppression of viral loads with the AAV-antibody approach. Recruiting --> Active, not recruiting
- |||||||||| PGT121 / Gilead, IAVI, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Single-chain variable fragments of broadly neutralizing antibodies prevent HIV cell-cell transmission. (Pubmed Central) - Mar 5, 2022
We demonstrate that unlike IgG, scFv of bNAbs are able to neutralize cell-free and cell-associated virus with similar potency. These scFv, which show functional activity in the therapeutic range, may therefore be suitable for further development as passive immunity for HIV prevention.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Trial completion: 3BNC117 and 10-1074 in ART-treated Individuals (clinicaltrials.gov) - Feb 15, 2022
P1, N=26, Completed,
These scFv, which show functional activity in the therapeutic range, may therefore be suitable for further development as passive immunity for HIV prevention. Active, not recruiting --> Completed
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
Trial termination, Combination therapy: Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals (clinicaltrials.gov) - Feb 9, 2022
P1, N=27, Terminated,
Active, not recruiting --> Completed Completed --> Terminated; Coronavirus 2019 (COVID-19) pandemic
- |||||||||| PGT121 / Gilead, IAVI, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, elipovimab (GS-9722) / Gilead, Xencor
HIV ENVELOPE DIVERSITY AND SENSITIVITY TO bNAbs ACROSS STAGES OF ACUTE AND EARLY HIV ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_871;
Similarly, susceptibility to bNAbs did not differ by stage of AEHI before or after ART. Collectively, these data argue against major differences in HIV diversity or bNAb sensitivity across AEHI stage or following more than one year of suppressive ART and suggest individuals who initiate ART during AEHI as a desirable population for bNAb treatment or cure trials.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
MUTATIONAL LANDSCAPE OF 10-1074 AND 3BNC117 SENSITIVITY IN A UK POPULATION WITH PHI ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_553;
Our findings show that around half the cohort treated during PHI has potential pre-existing resistance to 10-1074 and 3BNC117 based on current algorithms. Although it is unclear how well these algorithms predict clinical response to bNAbs in real world settings, the suggestion from these data is that screening may be key to guide effective treatment.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead
PERFORMANCE OF A PHENOTYPE AND 2 GENOTYPE ALGORITHMS FOR bNAb SENSITIVITY PREDICTION ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_552;
P2
We observed good agreement in bNAb sensitivity between the PhenoSense assay and both genotypic prediction algorithms for the V3-loop binding bNAb 10-1074. The agreement between phenotypic and genotypic sensitivity was lower for the CD4-binding site bNAb 3BNC117, which may pose greater challenges when screening participants for clinical studies and comparing results across different trials.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
SUSCEPTIBILITY TO 3BNC117 AND 10-1074 IN ART-SUPPRESSED CHRONICALLY INFECTED PERSONS ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_551;
This is a potential limitation of combining only two bnAbs as PREP or treatment, as a significant proportion of the circulating virus variants are likely to exhibit reduced susceptibility to at least one mAb. Further studies defining and validating the clinical correlates of bnAb susceptibility thresholds for therapeutic maintenance protocols and curative treatment strategies are urgently needed.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
PROLONGED VIRAL SUPPRESSION BY IMMUNOTHERAPY WITH ANTI-HIV ANTIBODIES 3BNC117/10-1074 ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_514;
P1
Furthermore, post-treatment control for 48 weeks and longer was observed in 12% of the study cohort. We are evaluating the immunomodulatory effects on the size and composition of the latent reservoir.
- |||||||||| 10-1074 / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
BEAT2: PEG-IFN-Α2B + 3BNC117 AND 10-1074 KEEPS HIV AT <20 C/ΜL DURING 26 WEEK ATI ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_505;
P1
We are currently evaluating step 3 effects on the HIV reservoir, as well as pharmacokinetics, immunological and virological parameters. These data will inform the next strategies to utilize bNAbs and interferon, alone or in combination in cure related strategies.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
ADMINISTRATION OF 3BNC117 AT ART INITIATION INDUCES LONG-TERM HIV CD8 T-CELL IMMUNITY ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_369;
P2
However, the frequency of Gag-specific CD8+ T cells was significantly higher in individuals that received 3BNC117 (with or without RMD) at 3 months after starting ART compared to ART control group (median 0.69% vs 0.29%, respectively, p=0.04) and at 12 months of ART (median 0.91% vs 0.31% respectively, p=0.03). Our results suggest that bNAb therapy at the time of ART initiation may have a vaccinal effect by inducing long-lasting Gag-specific T CD8+ cells responses, which have been associated with immune mediated virus control.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, Istodax (romidepsin) / Astellas, BMS
THE IMPACT OF 3BNC117 AND ROMIDEPSIN TREATMENT AT ART INITIATION ON HIV-1 PERSISTENCE ([VIRTUAL]) - Feb 7, 2022 - Abstract #CROI2022CROI_299;
P2
Co-administration of 3BNC117 at the time of ART initiation among HIV-1-infected individuals reduced the number of productively HIV-1-infected cells. Further, 3BNC117 with or without RMD during ATI initiation may lead to prolonged immunological control during ATI in individuals whose pre-ART viruses are sensitive to the bNAb.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Cell membrane-anchored anti-HIV single-chain antibodies and bifunctional inhibitors targeting the gp41 fusion protein: new strategies for HIV gene therapy. (Pubmed Central) - Jan 8, 2022
Fusion genes encoding the single-chain variable fragment (scFv) of 3BNC117, N6, PGT126, PGT128, 10E8, or 35O22 were constructed with a self-inactivating lentiviral vector, and they were efficiently expressed in the lipid raft sites of target cell membrane without affecting the expression of HIV-1 receptors (CD4, CCR5 and CXCR4)...In human CD4 T cells, GPI-10E8 and its bifunctional derivatives blocked both CCR5- and CXCR4-tropic HIV-1 isolates efficiently, and the modified cells displayed robust survival selection under HIV-1 infection. Therefore, our studies provide new strategies for generating HIV-resistant cells, which can be used alone or with other gene therapy approaches.
- |||||||||| 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead, elipovimab (GS-9722) / Gilead, Xencor
Clinical, Journal: Evaluation of Broadly Neutralizing Antibody Sensitivity by Genotyping and Phenotyping for Qualifying Participants to HIV Clinical Trials. (Pubmed Central) - Jan 1, 2022
The genotypic assessment was found to be as predictive as the direct measurement of bNAb sensitivity by phenotyping and may, therefore, be preferred because of more rapid turnaround time and assay simplicity. A significant number of the participants were predicted to have virus sensitive to EVM and 3BNC117 and could, thus, be potential participants for clinical trials involving these bNAbs.
- |||||||||| PGT121 / Gilead, IAVI, 3BNC117 / Rockefeller University, Cornell University, Frontier Biotech, Gilead
Journal: Combinations of Single Chain Variable Fragments From HIV Broadly Neutralizing Antibodies Demonstrate High Potency and Breadth. (Pubmed Central) - Dec 30, 2021
Using IC titers and concentrations of 1μg/mL, there was 93% coverage for one dual scFv combination (3BNC117+10E8v4), and 96% coverage for two of the triple combinations (CAP256.25+3BNC117+10E8v4 and PGT121+3BNC117+10E8v4). Combinations of scFv, therefore, show significantly improved breadth and potency over individual scFv and given their size advantage, have potential for use in passive immunization.
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