Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications

Qi Lei , Hongkui Deng , Shicheng Sun

Life Medicine ›› 2025, Vol. 4 ›› Issue (1) : lnaf002

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Life Medicine ›› 2025, Vol. 4 ›› Issue (1) : lnaf002 DOI: 10.1093/lifemedi/lnaf002
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Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications

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Abstract

Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation of human pluripotent stem cells (PSCs) emerges as a novel platform with the potential to generate an unlimited supply of therapeutic immune cells, especially when coupled with gene modification techniques. PSC-based immunotherapy is expected to meet the vast clinical demand for living drugs. Here, we examine recent preclinical and clinical advances in PSC-based immunotherapy, focusing on PSC gene modification strategies and differentiation methods for producing therapeutic immune cells. We also discuss opportunities in this field and challenges in cell quality and safety and stresses the need for further research and transparency to unlock the full potential of PSC immunotherapies.

Keywords

immunotherapy / pluripotent stem cells / off-the-shelf / gene-editing / differentiation

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Qi Lei, Hongkui Deng, Shicheng Sun. Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications. Life Medicine, 2025, 4(1): lnaf002 DOI:10.1093/lifemedi/lnaf002

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References

[1]

Maude SL , Frey N , Shaw PA , et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371: 1507- 17.

[2]

Maude SL , Laetsch TW , Buechner J , et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018; 378: 439- 48.

[3]

Schuster SJ , Bishop MR , Tam CS , et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019; 380: 45- 56.

[4]

Nastoupil LJ , Jain MD , Feng L , et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US lymphoma CAR T consortium. J Clin Oncol 2020; 38: 3119- 28.

[5]

Locke FL , Ghobadi A , Jacobson CA , et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol 2019; 20: 31- 42.

[6]

Locke FL , Miklos DB , Jacobson CA , et al; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med 2022; 386: 640- 54.

[7]

Wang Y , Jain P , Locke FL , et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US lymphoma CAR T consortium. J Clin Oncol 2023; 41: 2594- 606.

[8]

Wang M , Munoz J , Goy A , et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2020; 382: 1331- 42.

[9]

Abramson JS , Palomba ML , Gordon LI , et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 2020; 396: 839- 52.

[10]

Munshi NC , Anderson LD Jr. , Shah N , et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021; 384: 705- 16.

[11]

Jagannath S , Lin Y , Goldschmidt H , et al. KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma. Blood Cancer J 2021; 11: 116.

[12]

Martin T , Usmani SZ , Schecter JM , et al. Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin 2021; 37: 1779- 88.

[13]

Berdeja JG , Madduri D , Usmani SZ , et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 2021; 398: 314- 24.

[14]

Ying Z , Xie Y , Zheng W , et al. Efficacy and safety of relmacabtagene autoleucel, an anti-CD19 chimeric antigen receptor T cell, in relapsed/refractory B-cell non-Hodgkin’s lymphoma: 2-year results of a phase 1 trial. Bone Marrow Transplant 2023; 58: 288- 94.

[15]

Ying Z , Yang H , Guo Y , et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med 2021; 10: 999- 1011.

[16]

Keam SJ . Equecabtagene autoleucel: first approval. Mol Diagn Ther 2023; 27: 781- 7.

[17]

Qin C , Tian D-S , Zhou L-Q , et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduction Targeted Therapy 2023; 8: 5.

[18]

Wang Y , Wei X , Yan D , et al. Sustained remission and decreased severity of CAR T-cell related adverse events: a pivotal study report of CNCT19 (inaticabtagene autoleucel) treatment in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-Cell ALL) in China. Blood 2022; 140: 1598- 600.

[19]

Yang M , Zhang W , Yu K , et al. A novel BCMA CAR-T-cell therapy with optimized human scFv for treatment of relapsed/refractory multiple myeloma: results from phase I clinical trials. Haematologica 2022; 107: 1960- 5.

[20]

Gu R , Liu F , Zou D , et al. Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. J Hematol Oncol 2020; 13: 122.

[21]

Baker DJ , Arany Z , Baur JA , et al. CAR T therapy beyond cancer: the evolution of a living drug. Nature 2023; 619: 707- 15.

[22]

Harrison C . TCR cell therapies vanquish solid tumors — finally. Nat Biotechnol 2024; 42: 1477- 9.

[23]

Yamanaka S . Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell 2020; 27: 523- 31.

[24]

Shi Y , Inoue H , Wu JC , et al. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discovery 2017; 16: 115- 30.

[25]

Yoon DH , Cao J , Chen T-Y , et al. Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group. J Hematol Oncol 2020; 13: 21.

[26]

Tarazona R , Duran E , Solana R . Natural killer cell recognition of melanoma: new clues for a more effective immunotherapy. Front Immunol 2015; 6: 649.

[27]

Patel K , Rothman S , Das PA , et al. The ELiPSE-1 study: a phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies. J Clin Oncol 2023; 41: TPS7580- TPS7580.

[28]

Patel S , Patel M , Gutierrez M , et al. 755 Results of a phase I trial of FT500, a first-in-class, off-the-shelf, iPSC-derived NK cell therapy combined with PD-1/PD-L1 checkpoint blockade therapy and IL-2 in patients with advanced solid tumors. J ImmunoTher Cancer 2022; 10: A787- A787.

[29]

Therapeutics, F . A Phase I study of FT516 as monotherapy in relapsed/refractory acute myelogenous leukemia and in combination with monoclonal antibodies in relapsed/refractory B-cell lymphoma; NCT04023071; clinicaltrials. gov: October 25 2023.

[30]

Patel K , Bachanova V , Goodman AM , et al. Phase I study of FT516, an off-the-shelf iPSC-derived NK cell therapy, in combination with Rituximab in patients with relapsed/refractory B-cell lymphoma. Blood 2021; 138: 3873.

[31]

Strati P , Bachanova V , Goodman A , et al. Preliminary results of a phase I trial of FT516, an off-the-shelf natural killer (NK) cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line expressing high-affinity, non-cleavable CD16 (hnCD16), in patients (pts) with relapsed/refractory (R/R) B-cell lymphoma (BCL). J Clin Oncol 2021; 39: 7541- 7541.

[32]

Goulding J , Hancock B , Blum R , et al. 204 Combining FT536, a pan-tumor targeting CAR NK cell therapy, with CD16 engagers provides a coordinated targeting strategy to overcome tumor heterogeneity. J ImmunoTher Cancer 2022; 10: A217.

[33]

Goulding J , Blum R , Hancock B , et al. Abstract 1591: FT536: Preclinical development of a novel off-the-shelf CAR-MICA/B NK cell immunotherapy combined with radiation and antibody treatments as a first-of-kind pan-cancer targeting strategy. Cancer Res 2021; 81: 1591- 1591.

[34]

Rezner B , Solchaga L , Reyes L , et al. cGMP mass production of FT538, a first-of-kind, off-the-shelf, multiplexed engineered natural killer cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell line. Blood 2020; 136: 25.

[35]

Janakiram M , Vij R , Siegel DS , et al. A phase I study of FT538, a first-of-kind, off-the-shelf, multiplexed engineered, iPSC-derived NK cell therapy as monotherapy in relapsed/refractory acute myelogenous leukemia and in combination with daratumumab or elotuzumab in relapsed/refractory multiple myeloma. Blood 2020; 136: 3- 3.

[36]

Cichocki F , Bjordahl R , Goodridge JP , et al. Quadruple gene-engineered natural killer cells enable multi-antigen targeting for durable antitumor activity against multiple myeloma. Nat Commun 2022; 13: 7341.

[37]

Goodridge JP , Bjordahl R , Mahmood S , et al. FT576: multi-specific off-the-shelf CAR-NK cell therapy engineered for enhanced persistence, avoidance of self-fratricide and optimized MAB combination therapy to prevent antigenic escape and elicit a deep and durable response in multiple myeloma. Blood 2020; 136: 4- 5.

[38]

Bachanova V , Ghobadi A , Patel K , et al. Safety and efficacy of FT596, a first-in-class, multi-antigen targeted, off-the-shelf, iPSC-derived CD19 CAR NK cell therapy in relapsed/refractory B-cell lymphoma. Blood 2021; 138: 823- 823.

[39]

Dhakal B , Berdeja JG , Gregory T , et al. Interim phase I clinical data of FT576 as monotherapy and in combination with daratumumab in subjects with relapsed/refractory multiple myeloma. Blood 2022; 140: 4586- 7.

[40]

Park JH , Jain N , Chen A , et al. A phase I study of FT819, a first-ofkind, off-the-shelf, iPSC-derived TCR-less CD19 CAR T cell therapy for the treatment of relapsed/refractory B-cell malignancies. Blood 2020; 136: 15- 6.

[41]

Jing R , Scarfo I , Najia MA , et al. EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity. Cell Stem Cell 2022; 29: 1181- 96.e6.

[42]

Iriguchi S , Yasui Y , Kawai Y , et al. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nat Commun 2021; 12: 430.

[43]

Schmitt TM , Zúñiga-Pflücker JC . Induction of T cell development from hematopoietic progenitor cells by Delta-like-1 in vitro. Immunity 2002; 17: 749- 56.

[44]

Seet CS , He C , Bethune MT , et al. Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat Methods 2017; 14: 521- 30.

[45]

Themeli M , Kloss CC , Ciriello G , et al. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat Biotechnol 2013; 31: 928- 33.

[46]

Maeda T , Nagano S , Ichise H , et al. Regeneration of CD8αβ T cells from T-cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity. Cancer Res 2016; 76: 6839- 50.

[47]

Minagawa A , Yoshikawa T , Yasukawa M , et al. Enhancing T cell receptor stability in rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy. Cell Stem Cell 2018; 23: 850- 8.e4.

[48]

Kawai Y , Kawana-Tachikawa A , Kitayama S , et al. Generation of highly proliferative, rejuvenated cytotoxic T cell clones through pluripotency reprogramming for adoptive immunotherapy. Mol Ther 2021; 29: 3027- 41.

[49]

van der Stegen SJC , Lindenbergh PL , Petrovic RM , et al. Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells. Nat Biomed Eng 2022; 6: 1284- 97.

[50]

Wang Z , McWilliams-Koeppen HP , Reza H , et al. 3D-organoid culture supports differentiation of human CAR+ iPSCs into highly functional CAR T cells. Cell Stem Cell 2022; 29: 515- 27.e8.

[51]

Dhatchinamoorthy K , Colbert JD , Rock KL . Cancer immune evasion through loss of MHC class I antigen presentation. Front Immunol 2021; 12: 636568.

[52]

Olson JA , Leveson-Gower DB , Gill S , et al. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood 2010; 115: 4293- 301.

[53]

Ng ES , Davis R , Stanley EG , et al. A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies. Nat Protocols 2008; 3: 768- 76.

[54]

Knorr DA , Ni Z , Hermanson D , et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl. Med. 2013; 2: 274- 83.

[55]

Delconte RB , Kolesnik TB , Dagley LF , et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 2016; 17: 816- 24.

[56]

Zhu H , Blum RH , Bernareggi D , et al. Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes in vivo persistence and enhances anti-tumor activity. Cell stem cell 2020; 27: 224- 37.e6.

[57]

Jing Y , Ni Z , Wu J , et al. Identification of an ADAM17 cleavage region in human CD16 (FcγRIII) and the engineering of a non-cleavable version of the receptor in NK cells. PLoS One 2015; 10: e0121788.

[58]

Woan KV , Kim H , Bjordahl R , et al. Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy. Cell Stem Cell 2021; 28: 2062- 75.e5.

[59]

Snyder KM , Dixon KJ , Davis Z , et al. iPSC-derived natural killer cells expressing the FcγR fusion CD64/16A can be armed with antibodies for multitumor antigen targeting. J ImmunoTher Cancer 2023; 11: e007280.

[60]

Snyder KM , Hullsiek R , Mishra HK , et al. Expression of a recombinant high affinity IgG Fc receptor by engineered NK cells as a docking platform for therapeutic mAbs to target cancer cells. Front Immunol 2018; 9: 2873.

[61]

Klichinsky M , Ruella M , Shestova O , et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020; 38: 947- 53.

[62]

Shah Z , Tian L , Li Z , et al. Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer. Cell Stem Cell 2024; 31: 803- 17.e6.

[63]

Lei A , Yu H , Lu S , et al. A second-generation M1-polarized CAR macrophage with antitumor efficacy. Nat Immunol 2024; 25: 102- 16.

[64]

Shen J , Lyu S , Xu Y , et al. Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity. Cell Stem Cell 2024; 31: 1003- 19.e9.

[65]

Wang X , Su S , Zhu Y , et al. Metabolic Reprogramming via ACOD1 depletion enhances function of human induced pluripotent stem cell-derived CAR-macrophages in solid tumors.Nat Commun 2023; 14: 5778.

[66]

Wang R , Zhu T , Hou B , et al. An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma. Mol Ther 2023; 31: 2376- 90.

[67]

Tsuchiya N , Zhang R , Iwama T , et al. Type I interferon delivery by iPSC-derived myeloid cells elicits antitumor immunity via XCR1+ dendritic cells. Cell Reports 2019; 29: 162- 75.e9.

[68]

Makino K , Long MD , Kajihara R , et al. Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling. J ImmunoTher Cancer 2022; 10: e003827.

[69]

Zhang R , Liu T-Y , Senju S , et al. Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells. Cancer Immunol Res 2015; 3: 668- 77.

[70]

Mashima H , Zhang R , Kobayashi T , et al. Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response. Oncoimmunology 2020; 9: 1814620.

[71]

Chang Y , Syahirah R , Wang X , et al. Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy. Cell Rep 2022; 40: 111128.

[72]

Chang Y , Cai X , Syahirah R , et al. CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy. Nat Commun 2023; 14: 2266.

[73]

Lai W , Xie H , Liu Y , et al. Human pluripotent stem cell-derived eosinophils reveal potent cytotoxicity against solid tumors. Stem Cell Rep 2021; 16: 1697- 704.

[74]

Ivanovs A , Rybtsov S , Ng ES , et al. Human haematopoietic stem cell development: from the embryo to the dish.Development (Cambridge, England) 2017; 144: 2323- 37.

[75]

Ditadi A , Sturgeon CM , Keller G . A view of human haematopoietic development from the Petri dish. Nat Rev Mol Cell Biol 2017; 18: 56- 67.

[76]

Sun S , Wijanarko K , Liani O , et al. Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells. Immunol Rev 2023; 315: 154- 70.

[77]

Kennedy M , Awong G , Sturgeon CM , et al. T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures. Cell Reports 2012; 2: 1722- 35.

[78]

Sturgeon CM , Ditadi A , Awong G , et al. Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells. Nat Biotechnol 2014; 32: 554- 61.

[79]

Sun S , Motazedian A , Li JY , et al. Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis. Nat Commun 2024; 15: 7698.

[80]

Ng ES , Azzola L , Bruveris FF , et al. Differentiation of human embryonic stem cells to HOXA+ hemogenic vasculature that resembles the aorta-gonad-mesonephros. Nat Biotechnol 2016; 34: 1168- 79.

[81]

Motazedian A , Bruveris FF , Kumar SV , et al. Multipotent RAG1+ progenitors emerge directly from haemogenic endothelium in human pluripotent stem cell-derived haematopoietic organoids. Nat Cell Biol 2020; 22: 60- 73.

[82]

Ng ES , Sarila G , Li JY , et al. Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells. Nat Biotechnol 2024.

[83]

Atkins MH , Scarfò R , McGrath KE , et al. Modeling human yolk sac hematopoiesis with pluripotent stem cells. J Exp Med 2022; 219: e20211924.

[84]

Trotman-Grant AC , Mohtashami M , De Sousa Casal J , et al. DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system. Nat Commun 2021; 12: 5023.

[85]

Vo LT , Kinney MA , Liu X , et al. Regulation of embryonic haematopoietic multipotency by EZH1. Nature 2018; 553: 506- 10.

[86]

Wu Y , Hirschi KK . Regulation of hemogenic endothelial cell development and function. Annu Rev Physiol 2021; 83: 17- 37.

[87]

Zhu Q , Gao P , Tober J , et al. Developmental trajectory of prehematopoietic stem cell formation from endothelium. Blood 2020; 136: 845- 56.

[88]

Uenishi GI , Jung HS , Kumar A , et al. NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells. Nat Commun 2018; 9: 1828.

[89]

Michaels YS , Edgar JM , Major MC , et al. DLL4 and VCAM1 enhance the emergence of T cell-competent hematopoietic progenitors from human pluripotent stem cells. Sci Adv 2022; 8: eabn5522.

[90]

Mohtashami M , Shah DK , Nakase H , et al. Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. J immunol (Baltimore, Md. : 1950) 2010; 185: 867- 76.

[91]

Montel-Hagen A , Seet CS , Li S , et al. Organoid-induced differentiation of conventional T cells from human pluripotent stem cells. Cell Stem Cell 2019; 24: 376- 89.e8.

[92]

Shukla S , Langley MA , Singh J , et al. Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1. Nat Methods 2017; 14: 531- 8.

[93]

Edgar JM , Michaels YS , Zandstra PW . Multi-objective optimization reveals time- and dose-dependent inflammatory cytokinemediated regulation of human stem cell derived T-cell development. npj Regener Med 2022; 7: 11.

[94]

Prockop SE , Palencia S , Ryan CM , et al. Stromal cells provide the matrix for migration of early lymphoid progenitors through the thymic cortex. J Immunol (Baltimore, Md. : 1950) 2002; 169: 4354- 61.

[95]

Salomon DR , Crisa L , Mojcik CF , et al. Vascular cell adhesion molecule-1 is expressed by cortical thymic epithelial cells and mediates thymocyte adhesion. Implications for the function of alpha4beta1 (VLA4) integrin in T-cell development. Blood 1997; 89: 2461- 71.

[96]

Petrie HT , Zúñiga-Pflücker JC . Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol 2007; 25: 649- 79.

[97]

Calderón L , Boehm T . Synergistic, context-dependent, and hierarchical functions of epithelial components in thymic microenvironments. Cell 2012; 149: 159- 72.

[98]

Trampont PC , Tosello-Trampont A-C , Shen Y , et al. CXCR4 acts as a costimulator during thymic beta-selection. Nat Immunol 2010; 11: 162- 70.

[99]

Bosticardo M , Pala F , Calzoni E , et al. Artificial thymic organoids represent a reliable tool to study T-cell differentiation in patients with severe T-cell lymphopenia. Blood Adv 2020; 4: 2611- 6.

[100]

McAuley GE , Yiu G , Chang PC , et al. Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing. Cell 2023; 186: 1398- 416.e23.

[101]

Chang PC , Yuan X , Zampieri A , et al. Generation of antigen-specific mature T cells from RAG1-/-RAG2-/-B2M-/- stem cells by engineering their microenvironment. Nat Biomed Eng 2023; 8: 461- 78.

[102]

Woll PS , Martin CH , Miller JS , et al. Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity. J Immunol (Baltimore, Md. : 1950) 2005; 175: 5095- 103.

[103]

Sun JC , Lanier LL . NK cell development, homeostasis and function: parallels with CD8+ T cells. Nat Rev Immunol 2011; 11: 645- 57.

[104]

Li Y , Hermanson DL , Moriarity BS , et al. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 2018; 23: 181- 92.e5.

[105]

Cichocki F , Grzywacz B , Miller JS . Human NK cell development: one road or many? Front Immunol 2019; 10: 2078.

[106]

Chen Q , Ye W , Jian Tan W , et al. Delineation of natural killer cell differentiation from myeloid progenitors in human. Sci Rep 2015; 5: 15118.

[107]

Dege C , Fegan KH , Creamer JP , et al. Potently cytotoxic natural killer cells initially emerge from erythro-myeloid progenitors during mammalian development. Dev Cell 2020; 53: 229- 39.e7.

[108]

Lyadova I , Vasiliev A . Macrophages derived from pluripotent stem cells: prospective applications and research gaps. Cell Biosci 2022; 12: 96.

[109]

Sun S , See M , Nim HT , et al. Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection. Stem Cell Rep 2022; 17: 2156- 66.

[110]

Miyashita A , Fukushima S , Nakahara S , et al. Immunotherapy against metastatic melanoma with human iPS cell-derived myeloid cell lines producing type I interferons. Cancer Immunol Res 2016; 4: 248- 58.

[111]

Gutbier S , Wanke F , Dahm N , et al. Large-scale production of human iPSC-derived macrophages for drug screening. Int J Mol Sci 2020; 21: 4808.

[112]

Pouyanfard S , Meshgin N , Cruz LS , et al. Human induced pluripotent stem cell-derived macrophages ameliorate liver fibrosis. Stem Cells (Dayton, Ohio) 2021; 39: 1701- 17.

[113]

Ackermann M , Kempf H , Hetzel M , et al. Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections. Nat Commun 2018; 9: 5088.

[114]

Anderson DA 3rd , Dutertre CA , Ginhoux F , et al. Genetic models of human and mouse dendritic cell development and function. Nat Rev Immunol 2021; 21: 101- 15.

[115]

Sontag S , Förster M , Qin J , et al. Modelling IRF8 deficient human hematopoiesis and dendritic cell development with engineered iPS cells. Stem Cells (Dayton, Ohio) 2017; 35: 898- 908.

[116]

Sachamitr P , Leishman AJ , Davies TJ , et al. Directed differentiation of human induced pluripotent stem cells into dendritic cells displaying tolerogenic properties and resembling the CD141+ subset. Front Immunol 2017; 8: 1935.

[117]

Feucht J , Sun J , Eyquem J , et al. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nat Med 2019; 25: 82- 8.

[118]

Li S , Wang CS , Montel-Hagen A , et al. Strength of CAR signaling determines T cell versus ILC differentiation from pluripotent stem cells. Cell Reports 2023; 42: 112241.

[119]

Nishimura T , Kaneko S , Kawana-Tachikawa A , et al. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell 2013; 12: 114- 26.

[120]

Wakao H , Yoshikiyo K , Koshimizu U , et al. Expansion of functional human mucosal-associated invariant T cells via reprogramming to pluripotency and redifferentiation. Cell stem cell 2013; 12: 546- 58.

[121]

Zeng J , Tang SY , Wang S . Derivation of mimetic γδ T cells endowed with cancer recognition receptors from reprogrammed γδ T cell. PLoS One 2019; 14: e0216815.

[122]

Kitayama S , Zhang R , Liu TY , et al. Cellular adjuvant properties, direct cytotoxicity of re-differentiated Vα24 Invariant NKT-like cells from human induced pluripotent stem cells. Stem Cell Rep 2016; 6: 213- 27.

[123]

Li YR , Zhou Y , Kim YJ , et al. Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy. Cell Rep Med 2021; 2: 100449.

[124]

Zhu Y , Smith DJ , Zhou Y , et al. Development of hematopoietic stem cell-engineered invariant natural killer T cell therapy for cancer. Cell Stem Cell 2019; 25: 542- 57.e9.

[125]

Li Y-R , Zhou Y , Yu J , et al. Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method. Nat Biotechnol 2024.

[126]

Ruggeri A , Labopin M , Bacigalupo A , et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol 2018; 11: 40.

[127]

Martínez Bedoya D , Dutoit V , Migliorini D . Allogeneic CAR T cells: an alternative to overcome challenges of CAR T cell therapy in glioblastoma. Front Immunol 2021; 12: 640082.

[128]

Ren J , Liu X , Fang C , et al. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clinical Cancer Res 2017; 23: 2255- 66.

[129]

Kagoya Y , Guo T , Yeung B , et al. Genetic ablation of HLA Class I, Class II, and the T-cell receptor enables allogeneic T Cells to be used for adoptive T-cell therapy. Cancer Immunol Res 2020; 8: 926- 36.

[130]

Li W , Zhu X , Xu Y , et al. Simultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allorejection. Front Immunol 2022; 13: 1052717.

[131]

Gornalusse GG , Hirata RK , Funk SE , et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat Biotechnol 2017; 35: 765- 72.

[132]

Deuse T , Hu X , Gravina A , et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol 2019; 37: 252- 8.

[133]

Trounson A , Boyd NR , Boyd RL . Toward a universal solution: editing compatibility into pluripotent stem cells. Cell Stem Cell 2019; 24: 508- 10.

[134]

Wang B , Iriguchi S , Waseda M , et al. Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells. Nat Biomed Eng 2021; 5: 429- 40.

[135]

Doan AE , Mueller KP , Chen AY , et al. FOXO1 is a master regulator of memory programming in CAR T cells. Nature 2024; 629: 211- 8.

[136]

Chan JD , Scheffler CM , Munoz I , et al. FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy. Nature 2024; 629: 201- 10.

[137]

Zhang Y , He Y , Dai C , et al. Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy. Cell Rep Methods 2024; 44: 100843.

[138]

Melenhorst JJ , Chen GM , Wang M , et al. Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells. Nature 2022; 602: 503- 9.

[139]

Boulch M , Cazaux M , Cuffel A , et al. Tumor-intrinsic sensitivity to the pro-apoptotic effects of IFN-γ is a major determinant of CD4(+) CAR T-cell antitumor activity. Nat Cancer 2023; 4: 968- 83.

[140]

Singer A , Adoro S , Park JH . Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat Rev Immunol 2008; 8: 788- 801.

[141]

Yano H , Koga K , Sato T , et al. Human iPSC-derived CD4(+) Treg-like cells engineered with chimeric antigen receptors control GvHD in a xenograft model. Cell Stem Cell 2024; 31: 795- 802.e6.

[142]

Liu E , Tong Y , Dotti G , et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia 2018; 32: 520- 31.

[143]

Miller JS , Soignier Y , Panoskaltsis-Mortari A , et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005; 105: 3051- 7.

[144]

Vivier E , Tomasello E , Baratin M , et al. Functions of natural killer cells. Nat Immunol 2008; 9: 503- 10.

[145]

Soerens AG , Künzli M , Quarnstrom CF , et al. Functional T cells are capable of supernumerary cell division and longevity. Nature 2023; 614: 762- 6.

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