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. To address these challenges, this project aims to engineer hPSCs with synthetic chimeric antigen receptors (CARs) and develop novel platforms for scalable production of functional CAR-T and CAR-NK cells for targeted immunotherapy.

Start Date

01/01/2022 to 09/01/2022

Postdoc Qualifications

Eligible candidates should hold a Ph.D. in bioengineering or life science, or a related discipline before the starting date (flexible) of the post-doc position. Previous experience with stem cells, immunology, cancer biology or animal models is preferred but not required.

Co-Advisors

Xiaoping Bao, bao61@purdue.edu, Davidson School of Chemical Engineering, https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=210038
Qing Deng, qingdeng@purdue.edu, Department of Biological Sciences, https://www.bio.purdue.edu/lab/deng/

Bibliography

1. Chang Y, Hellwarth PB, Bao X. Fluorescent Indicators for Continuous and Lineage-Specific Reporting of Cell Cycle Phases in Human Pluripotent Stem Cells. Biotechnol Bioeng, 27352 (2020).
2. Hsu AY, Wang D, et al. Phenotypical microRNA screen reveals a noncanonical role of CDK2 in regulating neutrophil migration. Proc Natl Acad Sci USA, 116 (37): 18561-18570 (2019).
3. Bao X, et al. Gene Editing to Generate Versatile Human Pluripotent Stem Cell Reporter Lines for Analysis of Differentiation and Lineage Tracing. Stem Cells, 37 (12): 1556-1566 (2019).
4. Zhou W, Pal AS, et al. MicroRNA-223 Suppresses the Canonical NF-κB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation. Cell Rep, 22 (7): 1810-1823 (2018).
5. Bao X, et al. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat Biomed Eng, 1: 0003 (2016).