Biology subjects

Banik, D.

Publications and source records attributed to Banik, D..

3 recordsLinked to original sources

bioRxiv2026

Automated detection of Loa loa: a field trial in Cameroon

Onchocerciasis (river blindness) is targeted for elimination through mass administration (MDA) of ivermectin (IVM) to endemic populations. In areas where loiasis, caused by the blood-borne filarial parasite Loa loa, is co-endemic, IVM MDA faced significant challenges because individuals harboring more than 30,000 L. loa microfilaria (mf)/mL of blood are at high risk of developing serious adverse events (SAEs) that can sometimes be fatal. An alternative strategy was developed for safe IVM distribution: the so-called 'Test and Not Treat' (TaNT), which identifies and excludes individuals with high mf density from IVM MDA and treats only those with minimal risk. TaNT requires a point-of-care diagnostic device to rapidly quantify L. loa parasites in field conditions. The NTDscope is a handheld device which captures bright-field videos of whole blood in capillaries. An onboard algorithm detects and counts the live microfilaria of L. loa via movement of red blood cells. This paper describes (i) a new detection algorithm; and (ii) a May 2025 field trial in Cameroon using the NTDscope with new algorithm (550 patients). Results for the TaNT use case (i.e. flagging cases with L. loa mf densities > 30,000 mf/mL): 94% to 97% sensitivity, and 94% to 97% specificity. The results indicate that the NTDscope and new algorithm provide a greater margin of safety than the predecessor device, and can potentially offer rapid, effective field detection of high mf infections to enable scalability of the TaNT strategy.

pathology↗

bioRxiv2025

T-cell signaling relies on partial CD45-exclusion at sub-micron sized cellular contacts

How cell contact initiates T-cell activation is uncertain. The local exclusion of the receptor-type protein tyrosine phosphatase CD45 at cell contacts is believed to trigger immune receptor signaling but this is yet to be observed for T cells interacting with authentic cellular targets. Here, quantitative imaging of T cells interacting with tumor cells presenting either native or clinically relevant bi-specific TCR ligands, revealed that they form multiple sub-micron sized close contacts with their targets. The contacts were stabilised by the adhesion protein CD2, but efficient ligand detection required both CD2 and integrin ligation. CD45 was excluded from close contacts at the time of ZAP70 recruitment and signaling, but only partially (30- 40%). A single-cell, mass cytometric analysis showed that this change in kinase/phosphatase activity provoked strong T-cell activation and potent cytotoxicity via very small changes in signaling fluxes. Spatial stochastic simulations suggested that the proximal T-cell signaling network is optimised for efficient antigen discrimination in the setting of partial CD45 exclusion. Our work re-frames early T-cell activation as a process initiated by relatively subtle changes in kinase/phosphatase activity acting on small numbers of signaling effectors at minute cellular contacts.

immunology↗

bioRxiv2024

Imaging the interactions of chimeric antigen receptor-expressing T-cells with colorectal cancer cells

Chimeric antigen receptor (CAR) T-cell therapy has shown unprecedented success in haematological cancers but faces challenges in solid tumours. Although carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is differentially expressed in many solid tumours, anti-CEACAM5 CAR T-cells are ineffective. Here, we have studied the interaction of CEACAM5 targeting primary CAR T-cells with colorectal cancer (CRC) cells using fluorescence microscopy. We found that CRC cells glycocalyx is much deeper than that of the CAR T cell causing delayed activation. Oscillating calcium fluxes, indicative of non-sustained CAR T cell activation and reduced cytotoxicity, were observed when CAR T cells interacted with CRC cells, which increased with increasing cell-seeding time. Imaging revealed that this effect correlated with a progressive loss of accessible CEACAM5 antigen on the CRC cell surface, possibly due to their sequestration in the intercellular junction, rendering CAR T cell engagement less effective. Local proteolytic treatment with trypsin to disrupt the CRC cell monolayer, using a micropipette, increased CEACAM5 availability, decreased glycocalyx thickness, and restored sustained CAR T cell calcium fluxes, increasing the killing of CRC cells. Similar enhanced interaction was observed after treatment of CRC cell monolayer with hyaluronidase, approved for use in humans. We observed limited availability of CEACAM5 on human colorectal cancer tissues, whereas treatment with trypsin or hyaluronidase increased accessibility. Our results reveal why CAR T cells targeting CEACAM5 are ineffective and suggest possible routes to improved therapy for CRC.

immunology↗