PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cell Engineering”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1991

Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.

The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. We discuss the implications of these results in the context of Parkinson disease.

Animals↗
PubMed1990

Several aspects of red blood cell engineering: potential therapeutic applications.

Erythrocytes can be used to entrap drugs, enzymes or other molecules with active properties, with various encapsulation procedures. The method of internalization we are using includes an hypotonic dialysis step. Carrier erythrocytes survival depends on the dialysis process and the carried molecule. Research has led us to perform preclinical trials on animals for several drugs and enzyme therapies and for the improvement of oxyphoric capacity of erythrocytes. There exist many potential clinical applications for each kind of internalized molecules.

Animals↗
PubMed1987

Clonal analysis of antigen-specific interactions between T cells and genetically engineered B cells.

In order to investigate T cell-B cell interactions we constructed monoclonal, antigen-specific T- and B-cell populations. The Ia+ B-cell lymphoma A20-2J was transfected with trinitrophenyl (TNP)-specific heavy (mu) and light (kappa) chain Ig genes. A hapten-carrier complex (TNP-keyhole limpet hemocyanin (KLH)) bound to the surface Ig expressed on the transfectant and was presented to carrier-specific T-cell hybridoma clones at markedly low doses of antigen (0.01 microgram/ml) and in an Ia-restricted fashion. Two responses were elicited in the responding T-cell clones: (i) high levels of IL-2 secretion (320 units/ml), and (ii) cytotoxicity directed against the antigen-presenting B cell. This cytotoxicity was inhibited by D-mannose and was directed against innocent bystander cells, unlike cytotoxicity mediated by NK cells or alloreactive cytotoxic T lymphocyte. Helper and cytotoxic functions were often present in different T-cell hybridomas but some clones exhibited both activities. One representative T-cell hybridoma exhibited strong helper function for TNP-primed splenic B cells as detected in a plaque-forming cell assay, but was cytotoxic toward antigen-presenting B cells. Such monoclonal assay systems for studying cognate interactions of heterogeneous T cells and specific antigen-presenting cells will provide us with valuable new approaches for the study of antigen-specific T-cell regulation of B-cell activation in immune responses.

Animals↗
PubMed2026

A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.

Solid tumors often evade TCR-engineered αβ T cells when antigen expression varies or when the restricting Human Leukocyte Antigen (HLA) allele is lost. γδ T cells, in contrast, detect cellular dysregulation through non-peptide/Major Histocompatibility Complex (MHC) cues, including phosphoantigens and stress ligands, and can be developed as allogeneic therapies. Although intratumoral γδ T cell signatures are associated with improved outcome across cancers, γδ recognition itself is broad and still selected within the thymus just as αβ T cell receptors (TCRs) are. It does not, however, anchor specificity to a defined driver-mutation pMHC epitope. We therefore asked whether a high-affinity, co-receptor-independent αβ TCR could graft oncogenic-driver specificity onto γδ T cells while leaving the endogenous γδ TCR intact. We knocked the KRASG12V/HLA-A*11:01 TCR A11v into primary human γδ T cells. Engineered cells co-expressed the transgenic αβ TCR and the endogenous γδ TCR and lysed KRASG12V/HLA-A*11:01+ tumor cells in vitro and in vivo. To cover potential resistance through loss of HLA-A*11:01, we delivered an mRNA lipid nanoparticle (LNP) encoding a secreted mesothelin×CD3 (M5) bispecific T cell engager (TCE). LNP-M5 produced circulating TCE that redirected γδ A11v T cells and polyclonal bystander T cells to kill mesothelin+ targets, accompanied by development of higher γδ A11v T cell counts in vivo. In humanized mice bearing mixed HLA-A*11:01+ and HLA-A*11:01 - KRASG12V tumors, γδ A11v T cells produced transient control, whereas adding LNP-M5 yielded complete responses and prolonged survival. Thus, this two-part therapy couples invariant driver targeting to tunable redirection and addresses loss of the restricting HLA allele, a central escape route for TCR-based therapy. It provides an off-the-shelf reagent to enable KRAS-anchored treatment with the ability to redeliver the reagent.

Humans↗
PubMed2026

Nonviral transposon‑engineered stem cells characterization: dose‑dependency between vector copy number and transgene expression.

Genetically engineered stem cells hold substantial promises for advancing regenerative medicine, yet ensuring their genomic safety remains a critical challenge. A key safety concern is vector copy number (VCN), which defines the number of integrated transgene copies per genome. Although ddPCR is used to assess VCN in virally transduced cells, its application in transposon‑engineered systems is limited. In this study, we extended VCN determination to non‑viral, transposon‑engineered stem cells. In alignment with FDA recommendations, the primary objective was to establish a robust and quantitative framework for interim VCN determination at the time of lot release. Specifically, we demonstrate that reliable interim VCN estimates increase in a dose‑dependent manner with increasing plasmid input. In addition, strong linear correlations between VCN and both EGFP median fluorescence intensity (MFI) and gene‑of‑interest (GOI) protein expression validate the accuracy of this framework. Furthermore, comparison of two distinct GOIs revealed gene‑specific differences in expression efficiency. Together, these findings validate a standardized VCN determination workflow that quantitatively links plasmid dose, genomic integration, and functional transgene expression. This workflow provides a systematic characterization of engineered cells, offering comprehensive information to support downstream risk‑based analyses to ensure the genomic safety and stability of the final cell product.

Transgenes↗
PubMed2026

FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer.

FOXM1 is highly expressed in various cancer types and considered a key driver of cancer progression. Accordingly, we evaluated the immunogenicity of FOXM1 and investigated the feasibility of targeting this transcription factor using T-cell receptor (TCR) engineering. We identified epitopes derived from FOXM1 which were immunogenic on HLA-A*02:01, HLA-A*24:02, and HLA-A*23:01, endogenously processed and presented, and resulted in T-cell activation and cytotoxic T-cell responses. Following the generation of TCR-T cells, sensitivity and specificity were confirmed by peptide dose-response and X-scan, respectively. Most importantly, adoptive transfer of TCR-engineered T cells led to a significant reduction in tumor growth, as well as significantly prolonged survival in a tumor-bearing immunocompromised murine model. Our studies confirm the immunogenicity of FOXM1 and feasibility of targeting this antigen using TCR engineering.

Forkhead Box Protein M1↗
PubMed1989

Seeding of intravascular stents with genetically engineered endothelial cells.

The use of intravascular stents may be limited by both local thrombosis and restenosis due to intimal proliferation. In an effort to provide solutions to these problems, we seeded stents with genetically engineered endothelial cells in vitro. Using retroviral-mediated gene transfer, we inserted the gene for either bacterial beta-galactosidase or human tissue-type plasminogen activator (t-PA) into cultured sheep endothelial cells. The endothelial cells were seeded onto stainless steel stents and grown until the stents were covered. Expression of intracellular beta-galactosidase and high level secretion of t-PA were demonstrated both before and after the transduced cells were seeded onto the stents. Eight stents were expanded by in vitro balloon inflation, with observation of the seeded endothelial layer both prior to and after expansion. Most of the endothelial cells remained on the stents after balloon inflation. We conclude that intravascular stents can be coated with a layer of genetically engineered endothelial cells that can be either specifically labeled or made to secrete high levels of a therapeutic protein. Much of the layer of genetically engineered cells remains after the expansion of the stent in vitro. In vivo implantation of stents coated with genetically engineered endothelial cells may allow 1) introduction of genetically engineered endothelial cells directly into the vascular wall and 2) improvement of stent function through localized delivery of anticoagulant, thrombolytic, or antiproliferative molecules.

Animals↗
PubMed1991

[Characteristics of human growth hormone produced by genetically engineered mammalian cells].

Saizen is human growth hormone produced by mammalian cells by genetic engineering. It is identical with hypophyseal GH as regards various physical and chemical parameters. A number of tests did not reveal an alien protein at the 1 ppm level, nor the presence of viruses, and the DNA level is below the detection range. According to these results Saizen is a highly purified growth hormone.

Growth Hormone↗
PubMed2025

Engineering B cells to Express Fully Customizable Antibodies with Enhanced Fc Functions.

Genome editing within the constant region of the immunoglobulin Heavy chain locus (IGH) can reprogram B cells to express Heavy chain only antibodies (HCAbs) containing custom antigen-recognition domains. HCAb-engineered cells express both surface B cell receptor (BCR) and secreted antibody isoforms and respond to antigen. By selecting alternate editing sites within IGH, we extended this approach to also allow customization of the constant (Fc) domain of the Heavy chain, producing HCAbs with enhanced effector functions or containing mutations to extend antibody half-life. We also introduced mutations to force obligate HCAb homodimers and prevent unwanted pairing with endogenous antibody chains. Finally, we showed that additional domains could be accommodated at the HCAb C-terminus and preferentially expressed in the secreted isoform. Together these data demonstrate the flexibility of the HCAb editing platform to express fully customized molecules that take advantage of the properties of B cells.

Journal Article↗
PubMed1990

Use of recombinant DNA technology for engineering mammalian cells to produce proteins.

The recent advances in molecular biology have merged with somatic cell genetics and cell biology to allow mammalian cells to be extremely useful for the expression of foreign genes. This chapter has focused primarily on the approaches and potential limitations to high-level expression of proteins in mammalian cells. Future developments will involve the modification of mammalian cells in order to increase the efficiency of the various steps in protein processing and secretion. The ability to genetically engineer mammalian cells to produce high levels of desired proteins is presently complemented by advances in biochemical engineering which involve the ability to grow mammalian cells in very large volumes or at very high densities with reduced serum requirements. As a result, the cost for production of gram quantities of a protein from a mammalian host cell are approaching the cost of proteins from a mammalian host cell are approaching the cost of proteins similarly derived from microbial systems with all the advantages that mammalian systems afford.

Animals↗
PubMed1992

New strategies for active immunotherapy with genetically engineered tumor cells.

While previous tumor vaccine strategies have shown intriguing results, clearcut efficacy has been difficult to establish in human trials. Recently, newer approaches have been developed in animal systems that modify tumor cells genetically so that they express new antigens or secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigen or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity.

Genes, MHC Class II↗
PubMed1991

Tissue engineering by cell transplantation using degradable polymer substrates.

This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.

Animals↗
PubMed1991

Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells.

Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined.

Animals↗
PubMed1991

Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids.

With the exception of L-DOPA pharmacological treatment in Parkinson's disease, the neurodegenerative diseases lack effective treatment. Previous studies of neurodegenerative diseases suggest that symptoms arise secondary to defects in local neuronal circuitry and cannot be treated effectively with systemic drug delivery. Therefore, a promising treatment is the application of fetal or genetically engineering cells which protect or replace neurons in deficient regions. Engineered cells can be derived from cell lines or grown from recipient host fibroblasts or other cells, then modified to produce and secrete substances at a specific area of the brain. A previous study using parallel intracerebral infusions of nerve growth factor and an excitotoxic amino acid into the rat striatum demonstrated a protective effect of nerve growth factor on neurons [Aloe L. (1987) Biotechnology 5, 1085-1086]. In order to further test this paradigm, we have utilized a biological delivery system of nerve growth factor by implanting fibroblasts into the rat striatum which secrete high levels of nerve growth factor, prior to infusing the neurotoxins quinolinate or quisqualate. Animals in this group had smaller lesions than did a group implanted with a similar non-nerve growth factor-producing graft. In addition, marked neuronal sparing was noted within areas of lesions in those animals containing a nerve growth factor-producing graft. These results indicate that implantation of genetically engineered nerve growth factor-secreting cells can be used to protect neurons at a specific target from excitotoxin-induced lesions.

Animals↗
PubMed2026

CERTOMICS: trusted single-cell multiomics pipeline for high-resolution profiling of adoptive cellular immunotherapies.

SUMMARY: Adoptive cellular immunontherapies, such as chimeric antigen receptor (CAR) T cell therapy, have transformed cancer treatment, yet challenges such as resistance, relapse, and high costs limit their efficacy and accessibility. A comprehensive understanding of cellular heterogeneity and molecular profiles is essential to improve these therapies. Advanced single-cell multiomics technologies have the power to analyze the complex interactions between CAR-engineered cells, immune cells, and tumor cells. However, standardized single-cell multiomics computational pipelines specifically tailored to CAR-engineered cell products are lacking. Due to the synthetic nature of CAR transgenes, additional steps for reliable identification and characterization of CAR-positive cells are required but not included in existing data-processing workflows. To address this, we present CERTOMICS, a Nextflow-based, CAR-aware pipeline offering enhanced CERTainty in immunophenotyping and data interpretation, tailored for single-cell multiOMICSprofiling of adoptive cellular immunotherapies. The pipeline standardizes processing 10x Genomics single-cell multiomics data and integrates CAR-specific identification and quality control. Additionally, a curated repository of CAR construct sequences and annotation data is provided, serving as an extensible resource to support the analysis and development of CAR T cell therapies. AVAILABILITY AND IMPLEMENTATION: Detailed documentation of this pipeline, along with a resource on latest FDA-approved CAR therapies is available on our website: https://fraunhofer-izi.github.io/Living-Drugs-Wiki/. The data underlying this article are available on GitHub at https://github.com/fraunhofer-izi/CERTOMICS. The code is also published on Zenodo at https://doi.org/10.5281/zenodo.18709693.

Multiomics↗