Syngeneic CAR T cells engineered for persistent delivery of desired proteins.

Mouse primary T cells have been engineered as a platform using chimeric antigen receptors (CARs) to induce the synthesis of desired proteins at the disease site. This approach allows for the use of immunocompetent syngeneic tumor models to evaluate the CAR T cells' function within the context of a fully functioning immune system. Current efforts to evaluate cell-based technologies typically rely on xenograft tumor models in immunodeficient mice, which provide early feasibility data but may not fully capture the immune effects present in the tumor microenvironment.

Engineered CD4 T cells for in vivo delivery of therapeutic proteins.

The CD4 T cell, when engineered with a chimeric antigen receptor (CAR) containing specific intracellular domains, has been transformed into a zero-order drug-delivery platform. This introduces the capability of prolonged, disease-specific engineered protein biologics production, at the disease site. Experimental findings demonstrate that CD4 T cells offer a solution when modified with a CAR that includes 4-1BB but excludes CD28 intracellular domain.

Primary T-cell-based delivery platform for in vivo synthesis of engineered proteins.

Primary T cell has been transformed into a that synthesizes complex biologics at the disease site with spatiotemporal resolution. This broadly applicable technology can circumvent toxicities due to systemic administration of biologics that necessitates the use of high doses and may diffuse to the healthy tissues. Its clinical translation, however, has been impeded by manufacturing bottlenecks.

Genetically engineered pair of cells for serological testing and its application for SARS-CoV-2.

We have developed a serology test platform for identifying individuals with prior exposure to specific viral infections and provide data to help reduce public health risks. The serology test composed of a pair of cell lines engineered to express either a viral envelop protein (Target Cell) or a receptor to recognize the Fc region of an antibody (Reporter Cell), that is, . The formation of an immune synapse, facilitated by the analyte antibody, resulted into a dual-reporter protein expression by the Reporter Cell.

Electrically regulated cell-based intervention for viral infections.

This work reports on an engineered cell that-when electrically stimulated-synthesizes a desired protein, that is, . The platform has been used to express interferon (IFN)-β as a universal antiviral protein. Compelling evidence indicates the inevitability of new pandemics and drives the need for a pan-viral intervention that may be quickly deployed while more specific vaccines are in development.

Combinatorial treatment with statins and niclosamide prevents CRC dissemination by unhinging the MACC1-β-catenin-S100A4 axis of metastasis.

Colorectal cancer (CRC) is the second-most common malignant disease worldwide, and metastasis is the main culprit of CRC-related death. Metachronous metastases remain to be an unpredictable, unpreventable, and fatal complication, and tracing the molecular chain of events that lead to metastasis would provide mechanistically linked biomarkers for the maintenance of remission in CRC patients after curative treatment. We hypothesized, that Metastasis-associated in colorectal cancer-1 (MACC1) induces a secretory phenotype to enforce metastasis in a paracrine manner, and found, that the cell-free culture medium of MACC1-expressing CRC cells induces migration.

Cell-Based Platform for Antigen Testing and Its Application for SARS-CoV-2 Infection.

We have engineered a cell that can be used for diagnosing active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Isolation of individuals with active infections offers an effective solution for mitigating pandemics. However, the implementation of this practice requires robust infrastructure for rapid and intuitive testing, which is currently missing in our communities.

NK-Cell Biofactory as an Off-the-Shelf Cell-based Vector for Targeted In Situ Synthesis of Engineered Proteins.

The NK-92MI, a fast-growing cytolytic cell line with a track record of exerting clinical efficacy, is transformed into a vector for synthesizing calibrated amounts of desired engineered proteins at our disease site, that is, NK-cell Biofactory. This provides an allogeneic option to the previously published T-cell-based living vector that is limited by high manufacturing cost and product variability. The modularity of this pathway, which combines a "target" receptor with an "effector" function, enables reprogramming of the NK-cell Biofactory to target diseases with specific molecular biomarkers, such as cancer, viral infections, or auto-immune disorders, and overcome barriers that may affect the advancement of NK-cell therapies.

Lentivirus Manufacturing Process for Primary T-Cell Biofactory Production.

A process for maximizing the titer of lentivirus particles, deemed to be a necessity for transducing primary cells, is developed. Lentivirus particles, with a set of transgenes encoding an artificial cell-signaling pathway, are used to transform primary T cells as vectors for calibrated synthesis of desired proteins in situ, that is, T-cell biofactory cells. The process is also used to generate primary T cells expressing antigen-specific chimeric antigen receptors, that is, CAR T cells.

MACC1-the first decade of a key metastasis molecule from gene discovery to clinical translation.

Deciphering the paths to metastasis and identifying key molecules driving this process is one important issue for understanding and treatment of cancer. Such a key driver molecule is Metastasis Associated in Colon Cancer 1 (MACC1). A decade long research on this evolutionarily conserved molecule with features of a transcription factor as well as an adapter protein for versatile protein-protein interactions has shown that it has manifold properties driving tumors to their metastatic stage.

MACC1 regulates Fas mediated apoptosis through STAT1/3 - Mcl-1 signaling in solid cancers.

MACC1 was identified as a novel player in cancer progression and metastasis, but its role in death receptor-mediated apoptosis is still unexplored. We show that MACC1 knockdown sensitizes cancer cells to death receptor-mediated apoptosis. For the first time, we provide evidence for STAT signaling as a MACC1 target.

Human adult stem cells maintain a constant phenotype profile irrespective of their origin, Basal media, and long term cultures.

The study aims to identify the phenotypic marker expressions of different human adult stem cells derived from, namely, bone marrow, subcutaneous fat, and omentum fat, cultured in different media, namely, DMEM-Low Glucose, Alpha-MEM, DMEM-F12 and DMEM-KO and under long term culture conditions (>P20). We characterized immunophenotype by using various hematopoietic, mesenchymal, endothelial markers, and cell adhesion molecules in the long term cultures (Passages-P1, P3, P5, P9, P12, P15, and P20.) Interestingly, data revealed similar marker expression profiles irrespective of source, basal media, and extensive culturing.