Evaluation of the Immunomodulatory Effects of Radiation for Chimeric Antigen Receptor T Cell Therapy in Glioblastoma Multiforme.

Standard-of-care treatment for Glioblastoma Multiforme (GBM) is comprised of surgery and adjuvant chemoradiation. Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated disease-modifying activity in GBM and holds great promise. Radiation, a standard-of-care treatment for GBM, has well-known immunomodulatory properties and may overcome the immunosuppressive tumor microenvironment (TME); however, radiation dose optimization and integration with CAR T cell therapy is not well defined.

Rapid In Vitro Cytotoxicity Evaluation of Jurkat Expressing Chimeric Antigen Receptor using Fluorescent Imaging.

Chimeric antigen receptor (CAR) T cells are at the forefront of oncology. A CAR is constructed of a targeting domain (usually a single chain variable fragment, scFv), with an accompanying intra-chain linker, followed by a hinge, transmembrane, and costimulatory domain. Modification of the intra-chain linker and hinge domain can have a significant effect on CAR-mediated killing.

EGFR as a potent CAR T target in triple negative breast cancer brain metastases.

Purpose: There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo.

Investigation of human adipose-derived stem-cell behavior using a cell-instructive polydopamine-coated gelatin-alginate hydrogel.

Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)-treatment as a binding platform for bioactive compounds to create a versatile gelatin-alginate (Gel-Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose-derived stem cells (hASCs).

Investigating the Role of Polydopamine to Modulate Stem Cell Adhesion and Proliferation on Gellan Gum-Based Hydrogels.

Gellan gum-based hydrogels display limited cell adhesion ability due to the absence of cell-anchorage points usually present in proteins found in the extracellular matrix (ECM). This issue limits their use in the biomedical field as scaffolds to promote tissue repair. Our work addresses this challenge by investigating the use of polydopamine (pDA) as a bioactive layer to improve the surface and biological properties of gellan gum-based hydrogels cross-linked using carbodiimide chemistry.

Development of MicroRNA-146a-Enriched Stem Cell Secretome for Wound-Healing Applications.

Secretome-based therapies have the potential to become the next generation of viable therapeutic wound repair treatments. However, precise strategies aimed to refine and control the secretome composition are necessary to enhance its therapeutic efficacy and facilitate clinical translation. In this study, we aim to accomplish this by transfecting human adipose-derived stem cells (hASCs) with microRNA-146a, which is a potent regulator of angiogenesis and inflammation.

Fabrication of a Double-Cross-Linked Interpenetrating Polymeric Network (IPN) Hydrogel Surface Modified with Polydopamine to Modulate the Osteogenic Differentiation of Adipose-Derived Stem Cells.

Hydrogel surface properties can be modified to form bioactive interfaces to modulate the osteogenic differentiation of stem cells. In this work, a hydrogel made of gelatin methacrylamide (GelMA) and alginate was designed and tested as a scaffold to control stem-cell osteogenic differentiation. The hydrogel's surface was treated with polydopamine (pDA) to create an adhesive layer for the adsorption of the osteoinductive drug dexamethasone (Dex).