Biology subjects

Verschoore, M.

Publications and source records attributed to Verschoore, M..

3 recordsLinked to original sources

bioRxiv2026

Broadly neutralizing antibody-secreting CAR-T cells elicit Fc-mediated effector functions in vitro and suppress HIV in humanized mice

Despite significant advances in antiretroviral therapy (ART) that have transformed human immunodeficiency virus (HIV) infection from a fatal diagnosis to a manageable chronic condition, the persistent viral reservoir necessitates lifelong treatment underscoring the critical need for curative interventions. Viral persistence within anatomically distinct reservoirs, coupled with HIV-associated immune dysregulation accentuates the need for innovative combination immunotherapies that can act through multiple mechanisms. We introduce the Hybrid chimeric antigen receptor (CAR) platform: a dual-function immunotherapy that combines the targeted cytotoxicity of CAR-T cells with the secretion of broadly neutralizing antibodies (bNAbs). This approach enables direct elimination of HIV-infected cells, neutralization of free virus and Fc-mediated effector recruitment. In vitro, Hybrid CAR-T cells eliminated HIV-infected CD4+ T cells while the secreted bNAbs neutralized HIV and mediated robust Fc-effector functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In humanized mice, Hybrid CAR-T treatment achieved more than a 9-fold reduction in plasma viremia, accompanied by a significant decrease in viral levels across tissues, with circulating bNAbs detected in plasma. Collectively, these findings highlight the potential of Hybrid CAR-T cells as a synergistic next-generation therapeutic that bridges cellular and humoral immunity, supporting their translational promise as a strategy toward functional HIV cure.

immunology↗

bioRxiv2023

Integrative assessment of total and intact HIV-1 reservoir by a five-region multiplexed Rainbow digital PCR assay

Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive ART, hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Clinical trials have utilized two recent assays: intact proviral DNA assay (IPDA) and Q4PCR. While IPDA is more sensitive due to amplifying short fragments, it may overestimate intact fractions by relying only on two small regions. Q4PCR is sequencing-based and its performance might be subjected to bias against full-length proviruses. Leveraging digital PCR (dPCR) advancements, we developed the Rainbow 5-plex proviral HIV-1 DNA assay, assessing it with standard materials and samples from 69 PLWH. The Rainbow assay proved equally sensitive but more specific than IPDA, is not subjected to bias against full-length proviruses, enabling high-throughput quantification of total and intact reservoir size. This innovation offers potential for targeted evaluation and monitoring of rebound-competent reservoirs, contributing to HIV-1 management and cure strategies. TeaserThe 5 color HIV-1 Rainbow digital PCR assay offers a multi-level view on the HIV reservoir in one snapshot reaction.

molecular biology↗

bioRxiv2019

Pyk2 Overexpression in Postsynaptic Neurons Blocks Aβ1-42-induced Synaptotoxicity in a Microfluidic Co-Culture Model

Recent meta-analyses of genome-wide association studies identified a number of genetic risk factors of Alzheimers disease; however, little is known about the mechanisms by which they contribute to the pathological process. As synapse loss is observed at the earliest stage of Alzheimers disease, deciphering the impact of Alzheimers risk genes on synapse formation and maintenance is of great interest. In this paper, we report a microfluidic co-culture device that physically isolates synapses from pre- and postsynaptic neurons and chronically exposes them to toxic amyloid-beta (A{beta}) peptides secreted by model cell lines overexpressing wild-type or mutated (V717I) amyloid precursor protein (APP). Co-culture with cells overexpressing mutated APP exposed the synapses of primary hippocampal neurons to A{beta}1-42 molecules at nanomolar concentrations and induced a significant decrease in synaptic connectivity, as evidenced by distance-based assignment of postsynaptic puncta to presynaptic puncta. Treating the cells with antibodies that target different forms of A{beta} suggested that low molecular weight oligomers are the likely culprit. As proof of concept, we demonstrate that overexpression of protein tyrosine kinase 2 beta (Pyk2) -an Alzheimers disease genetic risk factor involved in synaptic plasticity and shown to decrease in Alzheimers disease brains at gene expression and protein levels-selectively in postsynaptic neurons is protective against A{beta}1-42-induced synaptotoxicity. In summary, our lab-on-a-chip device provides a physiologically-relevant model of Alzheimers disease-related synaptotoxicity, optimal for assessing the impact of risk genes in pre- and postsynaptic compartments.

neuroscience↗