Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer.

Immune cell therapy with chimeric antigen receptor (CAR) T cells, which has shown promising efficacy in patients with some hematologic malignancies, has introduced several successfully approved CAR T cell therapy products. Nevertheless, despite significant advances, treatment with these products has major challenges regarding potential toxicity and sometimes fatal adverse effects for patients. These toxicities can result from cytokine release or on-target off-tumor toxicity that targets healthy host tissue following CAR T cell therapy.

Characterization of CAR T Cells Manufactured Using Genetically Engineered Artificial Antigen Presenting Cells.

Objective: Chimeric antigen receptor (CAR) T cell therapy has recently emerged as a promising approach for the treatment of different types of cancer. Improving CAR T cell manufacturing in terms of costs and product quality is an important concern for expanding the accessibility of this therapy. One proposed strategy for improving T cell expansion is to use genetically engineered artificial antigen presenting cells (aAPC) expressing a membrane-bound anti-CD3 for T cell activation.

Generation and Functional Characterization of PLAP CAR-T Cells against Cervical Cancer Cells.

Chimeric antigen receptor (CAR) T-cell therapy is one of the cancer treatment modalities that has recently shown promising results in treating hematopoietic malignancies. However, one of the obstacles that need to be addressed in solid tumors is the on-target and off-tumor cytotoxicity due to the lack of specific tumor antigens with low expression in healthy cells. Placental alkaline phosphatase (PLAP) is a shared placenta- and tumor-associated antigen (TAA) that is expressed in ovarian, cervical, colorectal, and prostate cancers and is negligible in normal cells.

CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in -expanded human T cells.

B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation.

Toll-Like Receptor-Based Strategies for Cancer Immunotherapy.

Toll-like receptors (TLRs) are expressed and play multiple functional roles in a variety of immune cell types involved in tumor immunity. There are plenty of data on the pharmacological targeting of TLR signaling using agonist molecules that boost the antitumor immune response. A recent body of research has also demonstrated promising strategies for improving the cell-based immunotherapy methods by inducing TLR signaling.

Regulatory Roles of the Notch Signaling Pathway in Liver Repair and Regeneration: A Novel Therapeutic Target.

The liver is one of the significant regenerative organs in the body. Nevertheless, underlying molecular mechanisms regulating liver repair and regeneration following resection or damage remain largely unknown. The Notch signaling pathway is a profoundly evolutionarily well-conserved cell signaling system that mostly involves developing multicellular organisms.

An Easy and Fast Method for Production of Chinese Hamster Ovary Cell Line Expressing and Secreting Human Recombinant Activin A.

Objective: Growth factors are key elements of embryonic stem cell (ESC) research. Cell line development in eukaryotes is a time-consuming procedure which usually takes 12-18 months. Here, we report an easy and fast method with which production of Chinese hamster ovary (CHO) cells that express and secrete recombinant Activin A, as a major growth factor in endo/mesoderm differentiation of embryonic stem cells is achieved within 3-4 weeks.

Inclusion Body Expression and Refolding of Recombinant Bone Morphogenetic Protein-2.

Background: Bone Morphogenetic Protein-2 (BMP-2) is a cysteine rich growth factor expressed in homodimeric form and has a pivotal role in osteochondral development and fracture healing. Recent studies have benefited more from recombinant BMP-2 in osteochondral tissue engineering. Cost-effective and easy production at large scale makes () the first choice for recombinant protein expression programs.

Cloning, expression, and functional characterization of in-house prepared human leukemia inhibitory factor.

Objective: Leukemia inhibitory factor (LIF) plays important roles in cellular proliferation, growth promotion and differentiation of various types of target cells. In addition, LIF influences bone metabolism, cachexia, neural development, embryogenesis and inflammation. Human LIF (hLIF) is an essential growth factor for the maintenance of mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in a pluripotent, undifferentiated state.