Project Description

Cancer is a major threat for humans worldwide, with over 18 million new cases and 9.6 million cancer-related deaths in 2022. 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.

Start Date

Fall 2023/Spring 2024

Postdoc Qualifications

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

Co-Advisors

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

Short Bibliography

Chang Y, Deng Q, Bao X. A pluripotent road to immunoengineering. Nat Rev Bioeng (2023). https://doi.org/10.1038/s44222-023-00056-2.
Chang Y, Cai X, Syahirah R, Yao Y, Xu Y, Jin G, Bhute VJ, Torregrosa-Allen S, Elzey BD, Won Y, Deng Q, Lian X, Wang X, Eniola-Adefeso O, Bao X. CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemoimmunotherapy. Nature Communications 14, 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. Engineer Human Pluripotent Stem Cell-Derived Natural Killer Cells with PD-L1 Responsive Immunological Memory for Enhanced Immunotherapy Efficacy. Bioactive Materials (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 (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.