Engineering universal cells that evade immune detection

doi:10.1038/s41577-019-0200-1

Review

. 2019 Dec;19(12):723-733.

doi: 10.1038/s41577-019-0200-1. Epub 2019 Aug 15.

Engineering universal cells that evade immune detection

Robert Lanza¹, David W Russell², Andras Nagy^{3

4

5}

Affiliations

¹ Astellas Institute for Regenerative Medicine, Marlborough, MA, USA. robert.lanza@astellas.com.
² Universal Cells, Inc., Seattle, WA, USA.
³ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Ontario, Canada.
⁴ Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
⁵ panCELLa, Inc., Toronto, Ontario, Canada.

PMID: 31417198
DOI: 10.1038/s41577-019-0200-1

Review

Engineering universal cells that evade immune detection

Robert Lanza et al. Nat Rev Immunol. 2019 Dec.

. 2019 Dec;19(12):723-733.

doi: 10.1038/s41577-019-0200-1. Epub 2019 Aug 15.

Authors

Robert Lanza¹, David W Russell², Andras Nagy^{3

4

5}

Affiliations

¹ Astellas Institute for Regenerative Medicine, Marlborough, MA, USA. robert.lanza@astellas.com.
² Universal Cells, Inc., Seattle, WA, USA.
³ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Ontario, Canada.
⁴ Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
⁵ panCELLa, Inc., Toronto, Ontario, Canada.

PMID: 31417198
DOI: 10.1038/s41577-019-0200-1

Abstract

The prospect of transplanting cells and tissues without the risk of immune rejection or the need for powerful immunosuppressive drugs is the 'holy grail' of transplantation medicine. Now, with the advent of pluripotent stem cells, CRISPR-Cas9 and other gene-editing technologies, the race to create 'off-the-shelf' donor cells that are invisible to the immune system ('universal cells') has started. One important approach for creating such cells involves the manipulation of genes required for immune recognition, in particular HLA class I and II proteins. Other approaches leverage knowledge of immune-cloaking strategies used by certain bacteria, viruses, parasites, the fetus and cancer cells to induce tolerance to allogeneic cell-based therapies by modifying cells to express immune-suppressive molecules such as PD-L1 and CTLA4-Ig. Various academic groups as well as biotechnology and pharmaceutical companies are on the verge of bringing these therapies into the clinic.

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References

1. Brent, L. A History of Transplantation Immunology. (Academic Press, San Diego, 1996).
1. Min, D. I. & Monaco, A. P. Complications associated with immunosuppressive therapy and their management. Pharmacotherapy 11, 119S–125S (1991). - PubMed
1. Bix, M. et al. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349, 329–331 (1991). - PubMed
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1. Taylor, C. J. et al. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366, 2019–2025 (2005). - PubMed

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[1] Brent, L. A History of Transplantation Immunology. (Academic Press, San Diego, 1996).

[2] Brent, L. A History of Transplantation Immunology. (Academic Press, San Diego, 1996).

[3] Min, D. I. & Monaco, A. P. Complications associated with immunosuppressive therapy and their management. Pharmacotherapy 11, 119S–125S (1991). - PubMed

[4] Min, D. I. & Monaco, A. P. Complications associated with immunosuppressive therapy and their management. Pharmacotherapy 11, 119S–125S (1991). - PubMed

[5] Bix, M. et al. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349, 329–331 (1991). - PubMed

[6] Bix, M. et al. Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature 349, 329–331 (1991). - PubMed

[7] Liao, N. S., Bix, M., Zijlstra, M., Jaenisch, R. & Raulet, D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science 253, 199–202 (1991). - PubMed

[8] Liao, N. S., Bix, M., Zijlstra, M., Jaenisch, R. & Raulet, D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science 253, 199–202 (1991). - PubMed

[9] Taylor, C. J. et al. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366, 2019–2025 (2005). - PubMed

[10] Taylor, C. J. et al. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366, 2019–2025 (2005). - PubMed

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Engineering universal cells that evade immune detection

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