Biology subjects

Vyas, V.

Publications and source records attributed to Vyas, V..

5 recordsLinked to original sources

bioRxiv2025

Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy

Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. We applied an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) had increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR had high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induced metabolic reprogramming and enhanced anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission.

immunology↗

bioRxiv2022

Evaluation of the safety, immunogenicity and efficacy of a new live-attenuated lumpy skin disease vaccine in India

Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed using an Indian field strain (LSDV/India/2019/Ranchi). The virus was attenuated by continuous passage (P=50) in Vero cells. The vaccine (50th LSDV passage in Vero cells, named as Lumpi-ProVacInd) did not induce any local or systemic reaction upon its experimental inoculation in calves (n=10). At day 30 post-vaccination (pv), the vaccinated animals were shown to develop antibody- and cell-mediated immune response and exhibited complete protection upon virulent LSDV challenge. We observed a minimum Neethling response (0.018% animals; 5 out of 26940 animals) of the vaccine in field trials among 26940 animals. There was no significant reduction in the milk yield in lactating animals (n=10108), besides there was no abortion or any other reproductive disorder in the pregnant animals (n=2889). Sero-conversion was observed in 85.18% animals in the field by day 30 pv.

microbiology↗

bioRxiv2022

Dexamethasone Enhances CAR T Cell Persistence and Function by Upregulating Interleukin 7 Receptor

Dexamethasone (dex) is a glucocorticoid that is a mainstay for treatment of inflammatory pathologies, including immunotherapy-associated toxicities. Dex suppresses the endogenous immune response and is also believed to suppress the function of chimeric antigen receptor (CAR) T cells. However, recent reports observed higher CAR T cell numbers in patients treated with dex, highlighting the rationale for interrogating the specific effects of dex on CAR T cells. Here, we found that dex did not inhibit CAR T cell expansion or function. A single dose of dex during the manufacturing process upregulated the pro-persistence interleukin 7 receptor (IL7R) on CAR T cells and induced expression of genes involved in activation, migration, and persistence. The ex vivo upregulation of IL7R induced by dex significantly enhanced CAR T cell persistence and anti-tumor efficacy in vivo when combined with exogenous IL-7. Moreover, the combination of dex and IL-7 resulted in increased persistence of CAR T cells and led to complete remission of mice. Overall, our studies in both in vitro and in vivo treatment support a positive role of dex on CAR T cell potency and provide insight into the application of glucocorticoids in cellular anti-cancer therapy.

immunology↗

bioRxiv2017

Depth Dependent Nanomechanical Analysis of Extracellular Matrix in Multicell Spheroids.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC=\"FIGDIR/small/193516_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (44K):\norg.highwire.dtl.DTLVardef@4ba6b3org.highwire.dtl.DTLVardef@ad3c2dorg.highwire.dtl.DTLVardef@149e92corg.highwire.dtl.DTLVardef@16b6e51_HPS_FORMAT_FIGEXP M_FIG C_FIG Nanomechanical investigation with Atomic Force Microscope has revealed new details regarding various nanomechanical heterogeneities for cells that are embedded in extracellular matrix in Multicellular spheroidal culture. This investigation sheds new insight into dynamic relationship of cells with their surrounding environment in tumors and 3D multicellular cultures.\n\nNanotechnology has revolutionized the field of cancer biology and has opened new avenues towards understanding nanomechanical variations in rapidly growing tumors. Over the last decade Atomic Force Microscope (AFM) has played an important role in understanding nanomechanical properties of various cancer cell lines. This study is focused on Lewis Lung Carcinoma Cell (LLC) tumors as 3D multicellular spheroid (MS). Such multicellular structures have enabled investigation of various components of tumors in-vitro. To better comprehend mechanical properties of cells and its surrounding extracellular matrix (ECM), depth dependent indentation measurements were conducted with Atomic Force Microscope (AFM). Force-vs-indentation curves were used to create stiffness profiles as function of depth. Here studies were focused on outer most layer i.e. proliferation zone of the spheroid. AFM investigations of sample a MS revealed three nanomechanical topographies, Type A- high modulus due to collagen stress fibers, Type B- high stiffness at cell membrane & ECM interface and Type C - increased modulus due to cell lying deep inside matrix at the a depth of 1.35 microns. Various nanomechanical heterogeneities revealed in this investigation can shed new light in developing correct dosage regime for various tumor dissolving drugs and designing more controlled artificial extracellular matrix systems for replicating tissue growth in-vitro.\n\nShort Statistical SummaryThis article describes nanomechanical characteristics of the cells embedded in extracellular matrix in a multicellular spheroid. The paper contains 6350 words including title page and references. Graphical Content contains 46 words. This article contains 6 Figures and zero tables.

bioengineering↗

bioRxiv2017

Dynamic and Depth Dependent Nanomechanical Properties of Dorsal Ruffles in Live Cells and Biopolymeric Hydrogels

The nanomechanical properties of various biological and cellular surfaces are increasingly investigated with Scanning Probe Microscopy. Surface stiffness measurements are currently being used to define metastatic properties of various cancerous cell lines and other related biological tissues. Here we present a unique methodology to understand depth dependent nanomechanical variations in stiffness in biopolymers and live cells. In this study we have used A2780 & NIH3T3 cell lines and 0.5% & 1% Agarose to investigate depth dependent stiffness and porosity on nanomechanical properties in different biological systems. This analytical methodology can circumvent the issue associated with the contribution of substrates on cell stiffness. Here we demonstrate that by calculating continuous-step-wise-modulus on force vs. distance curves one can observe minute variation as function of depth. Due to the presence of different kinds of cytoskeletal filament, dissipation of contact force might vary from one portion of a cell to another. On NIH3T3 cell lines, stiffness profile of Circular Dorsal Ruffles could be observed in form of large parabolic feature with changes in stiffness at different depth. In biopolymers like agarose, depending upon the extent of polymerization in there can be increase or decrease in stiffness due variations in pore size and extent to which crosslinking is taking place at different depths. 0.5% agarose showed gradual decrease in stiffness whereas with 1% agarose there was slight increase in stiffness as one indents deeper into its surface.

biophysics↗