Project Description

Cancer is a major threat for humans worldwide, with over 18 million new cases and 9.6 million cancer-related deaths in 2019. Although most common cancer treatments include surgery, chemotherapy, and radiotherapy, unsatisfactory cure rates require new therapeutic approaches. Recently, adoptive cellular immunotherapies with chimeric antigen receptor (CAR) engineered T and natural killer (NK) cells have shown impressive clinical responses in patients with various blood and solid cancers. However, current clinical practices are limited by the need of large numbers of healthy immune cells, resistance to gene editing, lack of in vivo persistence, and a burdensome manufacturing strategy that requires donor cell extraction, modulation, expansion, and re-introduction per each patient. The ability to generate universally histocompatible and genetically-enhanced immune cells from continuously renewable human pluripotent stem cell (hPSC) lines offers the potential to develop a true off-the-shelf cellular immunotherapy. While functional CAR-T and NK cells have been successfully derived from hPSCs, a significant gap remains in the scalability, time-consuming (5 or more weeks), purity and robustness of the differentiation methods due to the cumbersome use of serum, and/or feeder cells, which will incur potential risk for contamination and may cause batch-dependency in the treatment. This project thus aims to develop a novel, chemically-defined platform for robust production of CAR-T and CAR-NK cells from hPSCs, and use machine learning algorithms to develop optimized CAR constructs. The postdoc recruited will help to engineer stem cells with gene editing tools, differentiate stem cells into immune cells, and perform molecular and cellular assays to characterize the cells.

Start Date

03/01/2025

Post Doc Qualifications

Candidates with background in life science, bioengineering, or a related field are encouraged to contact us. Previous experience with stem cells, immunology, cancer biology or animal models is a plus. 

Co-Advisors

Can Li, canli@purdue.edu, Davidson School of Chemical Engineering, https://canli1.github.io/

Qing Deng, qingdeng@purdue.edu, Department of Biological Sciences, https://www.bio.purdue.edu/lab/deng/ 

Bibliography

Chang Y, Cai X, Syahirah R, Yao Y, Xu Y, Jin G, Bhute VJ, Torregrosa-Allen S, Elzey BD, Won Y-Y, Deng Q, Lian XL*, Wang X*, Eniola-Adefeso O*, Bao X*. CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy. Nat Commun 14(1): 2266 (2023). https://www.nature.com/articles/s41467-023-37872-4.
Chang Y, Jin G, Luo W, Luo Q, Jung J, Hummel SN, Torregrosa-Allen S, Elzey BD, Low PS*, Lian X*, Bao X*. Engineered human pluripotent stem cell-derived natural killer cells with PD-L1 responsive immunological memory for enhanced immunotherapeutic efficacy. Bioact Mater 27: 168-180 (2023). https://www.sciencedirect.com/science/article/pii/S2452199X23001123.
Chang Y, Syahirah R, Wang X, Jin G, Torregrosa-Allen S, Elzey BD, Hummel SN, Wang T, Lian X*, Deng Q*, Broxmeyer HE, Bao X*. Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy. Cell Reports 40(3), 111128 (2022). https://doi.org/10.1016/j.celrep.2022.111128.
Chang Y, Syahirah R, Oprescu SN, Wang X, Jung J, Cooper SH, Torregrosa-Allen S, Elzey BD, Hsu AY, Randolph LN, Sun Y, Kuang S, Broxmeyer HE, Deng Q*, Lian X*, Bao X*. Chemically-defined generation of human hemogenic endothelium and definitive hematopoietic progenitor cells. Biomaterials. 285, 121569 (2022). https://www.sciencedirect.com/science/article/abs/pii/S0142961222002095.