Unlocking the Potential of IPSC-derived Immune Cells: Engineering INK and IT Cells for Cutting-edge Immunotherapy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Sep 16

PMID 39281684

Authors

Minggang Fang

Alexander Allen

Chong Luo

Jonathan D Finn

Affiliations

Soon will be listed here.

Abstract

Induced pluripotent stem cells (iPSCs) have emerged as a revolutionary tool in cell therapies due to their ability to differentiate into various cell types, unlimited supply, and potential as off-the-shelf cell products. New advances in iPSC-derived immune cells have generated potent iNK and iT cells which showed robust killing of cancer cells in animal models and clinical trials. With the advent of advanced genome editing technologies that enable the development of highly engineered cells, here we outline 12 strategies to engineer iPSCs to overcome limitations and challenges of current cell-based immunotherapies, including safety switches, stealth edits, avoiding graft-versus-host disease (GvHD), targeting, reduced lymphodepletion, efficient differentiation, increased persistence, stemness, metabolic fitness, homing/trafficking, and overcoming suppressive tumor microenvironment and stromal cell barrier. With the development of advanced genome editing techniques, it is now possible to insert large DNA sequences into precise genomic locations without the need for DNA double strand breaks, enabling the potential for multiplexed knock out and insertion. These technological breakthroughs have made it possible to engineer complex cell therapy products at unprecedented speed and efficiency. The combination of iPSC derived iNK, iT and advanced gene editing techniques provides new opportunities and could lead to a new era for next generation of cell immunotherapies.

Citing Articles

Induced Pluripotent Stem Cells in Birds: Opportunities and Challenges for Science and Agriculture.

Zahoor N, Arif A, Shuaib M, Jin K, Li B, Li Z Vet Sci. 2024; 11(12).

PMID: 39729006 PMC: 11680093. DOI: 10.3390/vetsci11120666.

References

Zhao W, Lei A, Tian L, Wang X, Correia C, Weiskittel T . Strategies for Genetically Engineering Hypoimmunogenic Universal Pluripotent Stem Cells. iScience. 2020; 23(6):101162. PMC: 7270609. DOI: 10.1016/j.isci.2020.101162. View

Li Y, Rezvani K, Rafei H . Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer. Immunol Rev. 2023; 320(1):217-235. PMC: 10841677. DOI: 10.1111/imr.13255. View

Wang D, Quan Y, Yan Q, Morales J, Wetsel R . Targeted Disruption of the β2-Microglobulin Gene Minimizes the Immunogenicity of Human Embryonic Stem Cells. Stem Cells Transl Med. 2015; 4(10):1234-45. PMC: 4572902. DOI: 10.5966/sctm.2015-0049. View

Tran H, Wan Z, Sheard M, Sun J, Jackson J, Malvar J . TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells. Clin Cancer Res. 2016; 23(3):804-813. PMC: 5361893. DOI: 10.1158/1078-0432.CCR-16-1743. View

Fujisaki H, Kakuda H, Imai C, Mullighan C, Campana D . Replicative potential of human natural killer cells. Br J Haematol. 2009; 145(5):606-13. PMC: 2776622. DOI: 10.1111/j.1365-2141.2009.07667.x. View

De Smedt M, Taghon T, Van de Walle I, De Smet G, Leclercq G, Plum J . Notch signaling induces cytoplasmic CD3 epsilon expression in human differentiating NK cells. Blood. 2007; 110(7):2696-703. DOI: 10.1182/blood-2007-03-082206. View

Riolobos L, Hirata R, Turtle C, Wang P, Gornalusse G, Zavajlevski M . HLA engineering of human pluripotent stem cells. Mol Ther. 2013; 21(6):1232-41. PMC: 3677304. DOI: 10.1038/mt.2013.59. View

Johnsen A, Templeton D, Sy M, Harding C . Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis. J Immunol. 1999; 163(8):4224-31. View

Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S . Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy. Cell Stem Cell. 2018; 23(6):850-858.e4. DOI: 10.1016/j.stem.2018.10.005. View

10.

Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L . HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 1997; 276(5319):1719-24. DOI: 10.1126/science.276.5319.1719. View

11.

Bondanza A, Ciceri F, Bonini C . Application of donor lymphocytes expressing a suicide gene for early GVL induction and later control of GVH reactions after bone-marrow transplantation. Methods Mol Med. 2004; 109:475-86. DOI: 10.1385/1-59259-862-5:475. View

12.

Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F . Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol. 2009; 27(7):1122-9. DOI: 10.1200/JCO.2008.18.0463. View

13.

Baker D, Ali L, Saxena G, Pryce G, Jones M, Schmierer K . The Irony of Humanization: Alemtuzumab, the First, But One of the Most Immunogenic, Humanized Monoclonal Antibodies. Front Immunol. 2020; 11:124. PMC: 7034358. DOI: 10.3389/fimmu.2020.00124. View

14.

Takizawa H, Manz M . Macrophage tolerance: CD47-SIRP-alpha-mediated signals matter. Nat Immunol. 2007; 8(12):1287-9. DOI: 10.1038/ni1207-1287. View

15.

Zhao L, Teklemariam T, Hantash B . Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives. Stem Cell Res. 2014; 13(2):342-54. DOI: 10.1016/j.scr.2014.08.004. View

16.

Introna M, Barbui A, Bambacioni F, Casati C, Gaipa G, Borleri G . Genetic modification of human T cells with CD20: a strategy to purify and lyse transduced cells with anti-CD20 antibodies. Hum Gene Ther. 2000; 11(4):611-20. DOI: 10.1089/10430340050015798. View

17.

Wang X, Chang W, Wong C, Colcher D, Sherman M, Ostberg J . A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011; 118(5):1255-63. PMC: 3152493. DOI: 10.1182/blood-2011-02-337360. View

18.

van Wilgenburg B, Browne C, Vowles J, Cowley S . Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions. PLoS One. 2013; 8(8):e71098. PMC: 3741356. DOI: 10.1371/journal.pone.0071098. View

19.

Barros L, Couto S, da Silva Santurio D, Paixao E, Cardoso F, da Silva V . Systematic Review of Available CAR-T Cell Trials around the World. Cancers (Basel). 2022; 14(11). PMC: 9179563. DOI: 10.3390/cancers14112667. View

20.

Knorr D, Ni Z, Hermanson D, Hexum M, Bendzick L, Cooper L . Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med. 2013; 2(4):274-83. PMC: 3659832. DOI: 10.5966/sctm.2012-0084. View