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Blockade of CCR5 T Cell Accumulation in the Tumor Microenvironment Optimizes Anti-TGF-β/PD-L1 Bispecific Antibody.
Adv Sci (Weinh)
November 2024
Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, P. R. China.
Article Synopsis
- The study investigates the bispecific antibody YM101, which shows better results than anti-PD-L1 alone in fighting tumors, but still fails to completely eliminate tumors in mice, indicating other immunosuppressive factors in the tumor microenvironment (TME).
- Researchers used single-cell RNA sequencing (scRNA-seq) to analyze changes in the TME caused by YM101, discovering increased immune cell populations boosting antitumor activity, yet also finding immunosuppressive CCR5 T cells.
- To improve YM101's effectiveness, the researchers combined it with Maraviroc, a CCR5 antagonist, which reduced the harmful CCR5 T cells and enhanced the overall antitumor immune response, suggesting that targeting CCR5 could
Hybrid Virtual Screening Approach to Predict Novel Natural Compounds against HIV-1 CCR5.
J Phys Chem B
July 2024
Biophysics Dept. Faculty of Science, Cairo University, Giza 12613, Egypt.
Background: Human immunodeficiency virus (HIV) infection continues to pose a major global health challenge. HIV entry into host cells via membrane fusion mediated by the viral envelope glycoprotein gp120/gp41 is a key step in the HIV life cycle. CCR5, expressed on CD4+ T cells and macrophages, acts as a coreceptor facilitating HIV-1 entry.
View Article and Find Full Text PDFCross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.
Antivir Ther
December 2023
Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA.
Background: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.
Methods: The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated.
Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV.
Vaccines (Basel)
May 2023
Department of Microbiology and Immunology, Western University, London, ON N6A 3K7, Canada.
Vesicular stomatitis virus (VSV) remains an attractive platform for a potential HIV-1 vaccine but hurdles remain, such as selection of a highly immunogenic HIV-1 Envelope (Env) with a maximal surface expression on recombinant rVSV particles. An HIV-1 Env chimera with the transmembrane domain (TM) and cytoplasmic tail (CT) of SIVMac239 results in high expression on the approved Ebola vaccine, rVSV-ZEBOV, also harboring the Ebola Virus (EBOV) glycoprotein (GP). Codon-optimized (CO) Env chimeras derived from a subtype A primary isolate (A74) are capable of entering a CD4+/CCR5+ cell line, inhibited by HIV-1 neutralizing antibodies PGT121, VRC01, and the drug, Maraviroc.
View Article and Find Full Text PDFEffects of chemokine (C-C motif) receptor 2 and 3 antagonists in rat models of hemorrhagic shock.
PLoS One
April 2023
Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
Systemic concentrations of chemokine CCL2, an agonist at chemokine receptors CCR2/3/5, have been associated with hemodynamic instability after traumatic-hemorrhagic shock. We reported previously that the CCR2 antagonist INCB3284 prevents cardiovascular collapse and reduces fluid requirements after 30min of hemorrhagic shock (HS), whereas the CCR5 antagonist Maraviroc was ineffective. The effects of CCR3 blockade after HS are unknown and information on the therapeutic potential of INCB3284 after longer periods of HS and in HS models in the absence of fluid resuscitation (FR) is lacking.
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