Medicine and Health Sciences Commons^™

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

Human Gucy2c-Targeted Chimeric Antigen Receptor (Car)-Expressing T Cells Eliminate Colorectal Cancer Metastases., Michael S. Magee, Tara S. Abraham, Trevor R. Baybutt, John C. Flickinger, Natalie A. Ridge, Glen P Marszalowicz, Priyanka Prajapati, Adam R. Hersperger, Scott A. Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting …

Protection Effect Of Exogenous Fibroblast Growth Factor 21 On The Kidney Injury In Vascular Calcification Rats, Yu-Chen Shi, Wei-Wei Lu, Yue-Long Hou, Kun Fu, Feng Gan, Shu-Juan Cheng, Shao-Ping Wang, Yong-Fen Qi, Jing-Hua Liu

Pharmacology and Nutritional Sciences Faculty Publications

Background: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats.

Methods: The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …