PLOS PATHOGENS
Rachel S. Leibman, Max W. Richardson, Christoph T. Ellebrecht, Colby R. Maldini, Joshua A. Glover, Anthony J. Secreto, Irina Kulikovskaya, Simon F. Lacey, Sarah R. Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A. Dufendach, Michael C. Holmes, Ronald G. Collman, Aimee S. Payne, James L. Riley
PLOS Pathogens
DOI: 10.1371/journal.ppat.1006613
Abstract:
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy.
Related Posts
Neurology
Comparative Spatial Analyses of the Tumor Immune Landscape in Mouse Models of Glioblastoma Using the PhenoCode Discovery Mouse Neuro Panel and Customized Markers
Poster Background Developing effective therapies for glioblastoma (GBM) relies on robust preclinical animal models that enable detailed investigation of tumor biology, discovery of therapeutic targets, and evaluation of new treatment…
Oncology
Development of a Spatial Metabolic Map of Immunotherapy Sensitive and Resistant Cutaneous Skin Carcinoma
Poster Background Ultrahigh-Plex Single-cell Spatial Phenotyping has revealed valuable insights into the tumor immune microenvironment (TiME) for biomarker discovery and stratification of clinical responses. Metabolic reprogramming is a key hallmark…
Spatial Immunometabolic Profiling of Non-Small Cell Lung Cancer Reveals Distinct Immune Exclusion Patterns and Functional Niches
Analytical validation of a multiplex immunofluorescence 7-Biomarker Immunoprint® assay on the Akoya PhenoImager HT platform for stage I/II Melanoma
Neurology
Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study
Alzheimer’s Research and Therapy | August 26, 2024 Sampani K, Ness S, Tuz-Zahra F, Aytan N, Spurlock EE, Alluri S, Chen X, Siegel NH, Alosco ML, Xia W, Tripodis Y,…
Neurology
Clinical validation of the LucentAD p-Tau 217 as a lab developed test (LDT) for clinical use
Poster The intersection of new therapeutic options for Alzheimer’s disease (AD), the emergence of accurate blood-based tests for AD, and the anticipated health system log jam for confirmatory diagnostic testing…
Neurology
Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice
Alzheimer’s & Dementia | August 3, 2024 Verberk IMW, Jutte J, Kingma MY, Vigneswaran S, Gouda MMTEE, van Engelen MP, Alcolea D, Arranz J, Fortea J, Lleó A, Chevalier C,…
Neurology
Discovering novel plasma biomarkers for ischemic stroke: Lipidomic and metabolomic analyses in an aged mouse model
Journal of Lipid Research | August 2, 2024 Becktel DA, Frye JB, Le EH, Whitman SA, Schnellmann RG, Morrison HW, Doyle KP. J Lipid Res. 2024 https://doi.org/10.1016/j.jlr.2024.100614 Abstract Ischemic stroke…