PMID- 37922880
OWN - NLM
STAT- MEDLINE
DCOM- 20231107
LR  - 20240322
IS  - 1875-9777 (Electronic)
IS  - 1875-9777 (Linking)
VI  - 30
IP  - 11
DP  - 2023 Nov 2
TI  - Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives 
      from innate immune cell cytotoxicity.
PG  - 1538-1548.e4
LID - S1934-5909(23)00365-X [pii]
LID - 10.1016/j.stem.2023.10.003 [doi]
AB  - Immune rejection of allogeneic cell therapeutics remains a major problem for 
      immuno-oncology and regenerative medicine. Allogeneic cell products so far have 
      inferior persistence and efficacy when compared with autologous alternatives. 
      Engineering of hypoimmune cells may greatly improve their therapeutic benefit. We 
      present a new class of agonistic immune checkpoint engagers that protect human 
      leukocyte antigen (HLA)-depleted induced pluripotent stem cell-derived 
      endothelial cells (iECs) from innate immune cells. Engagers with agonistic 
      functionality to their inhibitory receptors TIM3 and SIRPalpha effectively protect 
      engineered iECs from natural killer (NK) cell and macrophage killing. The SIRPalpha 
      engager can be combined with truncated CD64 to generate fully immune evasive iECs 
      capable of escaping allogeneic cellular and immunoglobulin G (IgG) 
      antibody-mediated rejection. Synthetic immune checkpoint engagers have high 
      target specificity and lack retrograde signaling in the engineered cells. This 
      modular design allows for the exploitation of more inhibitory immune pathways for 
      immune evasion and could contribute to the advancement of allogeneic cell 
      therapeutics.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Gravina, Alessia
AU  - Gravina A
AD  - Transplant and Stem Cell Immunobiology (TSI)-Lab, Department of Surgery, 
      University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 
      94143, USA.
FAU - Tediashvili, Grigol
AU  - Tediashvili G
AD  - Transplant and Stem Cell Immunobiology (TSI)-Lab, Department of Surgery, 
      University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 
      94143, USA.
FAU - Zheng, Yueting
AU  - Zheng Y
AD  - Shinobi Therapeutics, 2 Tower Place, South San Francisco, CA 94080, USA.
FAU - Iwabuchi, Kumiko A
AU  - Iwabuchi KA
AD  - Shinobi Therapeutics, 2 Tower Place, South San Francisco, CA 94080, USA.
FAU - Peyrot, Sara M
AU  - Peyrot SM
AD  - Shinobi Therapeutics, 2 Tower Place, South San Francisco, CA 94080, USA.
FAU - Roodsari, Susan Z
AU  - Roodsari SZ
AD  - Shinobi Therapeutics, 2 Tower Place, South San Francisco, CA 94080, USA.
FAU - Gargiulo, Lauren
AU  - Gargiulo L
AD  - Shinobi Therapeutics, 2 Tower Place, South San Francisco, CA 94080, USA.
FAU - Kaneko, Shin
AU  - Kaneko S
AD  - Laboratory of Regenerative Immunotherapy, Department of Cell Growth and 
      Differentiation, Center for iPS cell Research, Kyoto University, Sakyo-ku, Kyoto, 
      Japan.
FAU - Osawa, Mitsujiro
AU  - Osawa M
AD  - Shinobi Therapeutics, Med-Pharm Collaboration Building 46-29, 
      Yoshida-Shimo-Adachi-Cho, Sakyo-Ku, Kyoto, Japan.
FAU - Schrepfer, Sonja
AU  - Schrepfer S
AD  - Transplant and Stem Cell Immunobiology (TSI)-Lab, Department of Surgery, 
      University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 
      94143, USA.
FAU - Deuse, Tobias
AU  - Deuse T
AD  - Transplant and Stem Cell Immunobiology (TSI)-Lab, Department of Surgery, 
      University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 
      94143, USA. Electronic address: tobias.deuse@ucsf.edu.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (HLA Antigens)
SB  - IM
CIN - Cell Stem Cell. 2023 Nov 2;30(11):1393-1394. PMID: 37922874
MH  - Humans
MH  - *Induced Pluripotent Stem Cells/metabolism
MH  - Endothelial Cells/metabolism
MH  - HLA Antigens
MH  - Killer Cells, Natural
MH  - Immunity, Innate
OTO - NOTNLM
OT  - hypoimmune editing
OT  - immune checkpoints
OT  - immune evasion
COIS- Declaration of interests UCSF has filed patent applications that cover inventions 
      of this study. Y.Z., K.A.I., S.M.P., S.Z.R., L.G., and M.O. are employees of 
      Shinobi Therapeutics and own stock; S.K. and T.D. are founders of Shinobi 
      Therapeutics and own stock. S.S. is currently an employee of Sana Biotechnology, 
      Inc. and S.S. and T.D. own stock in Sana Biotechnology, Inc. No materials or 
      funding was received from Sana Biotechnology, Inc. for use in this study
EDAT- 2023/11/06 03:54
MHDA- 2023/11/07 06:46
CRDT- 2023/11/03 19:25
PHST- 2022/12/19 00:00 [received]
PHST- 2023/08/23 00:00 [revised]
PHST- 2023/10/04 00:00 [accepted]
PHST- 2023/11/07 06:46 [medline]
PHST- 2023/11/06 03:54 [pubmed]
PHST- 2023/11/03 19:25 [entrez]
AID - S1934-5909(23)00365-X [pii]
AID - 10.1016/j.stem.2023.10.003 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2023 Nov 2;30(11):1538-1548.e4. doi: 10.1016/j.stem.2023.10.003.