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Article ; Online: Novel JAK Inhibitors to Reduce Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation in a Preclinical Mouse Model.

Kim, Sena / Ruminski, Peter / Singh, Megh / Staser, Karl / Ashami, Kidist / Ritchey, Julie / Lim, Sora / DiPersio, John F / Choi, Jaebok

Molecules (Basel, Switzerland)

2024 Volume 29, Issue 8

Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T ... ...

Abstract	Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies. We previously demonstrated that targeting JAK1/JAK2, mediators of interferon-gamma receptor (IFNGR) and IL-6 receptor signaling, in donor T cells using baricitinib and ruxolitinib results in a significant reduction in GvHD after allo-HCT. Furthermore, we showed that balanced inhibition of JAK1/JAK2 while sparing JAK3 is important for the optimal prevention of GvHD. Thus, we have generated novel JAK1/JAK2 inhibitors, termed WU derivatives, by modifying baricitinib. Our results show that WU derivatives have the potential to mitigate GvHD by upregulating regulatory T cells and immune reconstitution while reducing the frequencies of antigen-presenting cells (APCs) and CD80 expression on these APCs in our preclinical mouse model of allo-HCT. In addition, WU derivatives effectively downregulated CXCR3 and T-bet in primary murine T cells. In summary, we have generated novel JAK inhibitors that could serve as alternatives to baricitinib or ruxolitinib.
MeSH term(s)	Animals ; Mice ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/metabolism ; Azetidines/pharmacology ; Disease Models, Animal ; Graft vs Host Disease/prevention & control ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Janus Kinase 1/antagonists & inhibitors ; Janus Kinase 1/metabolism ; Janus Kinase 2/metabolism ; Janus Kinase 2/antagonists & inhibitors ; Janus Kinase Inhibitors/pharmacology ; Mice, Inbred C57BL ; Purines/pharmacology ; Pyrazoles/pharmacology ; Sulfonamides/pharmacology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/drug effects ; Transplantation, Homologous
Chemical Substances	baricitinib
Language	English
Publishing date	2024-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules29081801
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Article ; Online: Immunotherapy for T-Cell ALL and T-Cell NHL.

DiPersio, John F / Staser, Karl / Cooper, Matthew

Clinical lymphoma, myeloma & leukemia

2020 Volume 20 Suppl 1, Page(s) S56–S58

MeSH term(s)	Humans ; Immunotherapy/methods ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/immunology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology
Language	English
Publishing date	2020-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.1016/S2152-2650(20)30462-6
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Zs.A 5903: Show issues

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Article ; Online: Histopathologic and immunophenotypic features of cutaneous solid organ transplant-associated graft-vs-host disease: Comparison with acute hematopoietic cell transplant-associated graft-vs-host disease and cutaneous drug eruption.

Russell, Aaron J / Musiek, Amy C / Staser, Karl W / Rosman, Ilana S

Journal of cutaneous pathology

2021 Volume 48, Issue 12, Page(s) 1480–1488

Abstract: Background: Although it is relatively common after hematopoietic cell transplant (HCT), graft-vs-host disease (GVHD) is a rare complication following solid organ transplantation (SOT).: Methods: This study evaluated skin biopsy specimens from five ... ...

Abstract	Background: Although it is relatively common after hematopoietic cell transplant (HCT), graft-vs-host disease (GVHD) is a rare complication following solid organ transplantation (SOT). Methods: This study evaluated skin biopsy specimens from five cases of SOT GVHD, 15 cases of HCT GVHD, and 15 cases of cutaneous drug eruption. Immunohistochemical staining for CD3, CD4, CD8, T-bet, and GATA-3 was performed to examine the density and immune phenotype of skin-infiltrating lymphocytes. Results: Similar to HCT GVHD, the predominant histopathologic findings in skin biopsy specimens of SOT GVHD were widespread vacuolar interface dermatitis with scattered necrotic keratinocytes. However, the density of dermal inflammation was considerably higher in SOT GVHD. Features that were more predictive of a cutaneous drug eruption over GVHD included spongiosis, confluent parakeratosis, and many eosinophils. Involvement of the hair follicle epithelium was seen in all three disorders. Both forms of cutaneous GVHD showed a predominance of Th1 (CD3+/T-bet+) lymphocytes within the inflammatory infiltrates. This shift was more pronounced in SOT GVHD, particularly among intraepidermal T-cells. Conclusions: SOT GVHD shares many histopathologic features with HCT GVHD. However, SOT GVHD has a greater tendency to develop brisk lichenoid inflammation.
MeSH term(s)	Adult ; Aged ; Drug Eruptions/immunology ; Drug Eruptions/pathology ; Female ; Graft vs Host Disease/etiology ; Graft vs Host Disease/immunology ; Graft vs Host Disease/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Organ Transplantation/adverse effects ; Retrospective Studies
Language	English
Publishing date	2021-07-07
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.14093
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Zs.A 1043: Show issues

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Article ; Online: Research Techniques Made Simple: CAR T-Cell Therapy.

Siddiqi, Haziq F / Staser, Karl W / Nambudiri, Vinod E

The Journal of investigative dermatology

2018 Volume 138, Issue 12, Page(s) 2501–2504.e1

Abstract: Chimeric antigen receptor (CAR) and chimeric autoantibody receptor T-cell therapy hold great promise in the treatment of cancer and autoimmune disease, respectively. This powerful technique involves genetically engineering T lymphocytes to enable ... ...

Abstract	Chimeric antigen receptor (CAR) and chimeric autoantibody receptor T-cell therapy hold great promise in the treatment of cancer and autoimmune disease, respectively. This powerful technique involves genetically engineering T lymphocytes to enable selective destruction of disease-causing cells. In the current approach, a patient's T cells are genetically engineered to express an antigen-specific antibody fragment fused to activating cytoplasmic T-cell signaling domains. After ex vivo activation and genetic modification of a patient's own T cells, the individually tailored CAR T cells are then infused into the patient for the selective destruction of cells bearing the targeted antigen. CAR T cells directed against the CD19 antigen expressed on B lymphoma cells have shown remarkable clinical efficacy in the treatment of refractory lymphoma, with two anti-CD19 CAR-T products recently gaining approval from the US Food and Drug Administration. For dermatological disease, preliminary studies have shown efficacy of CAR T cells in targeting melanoma cells and the pathogenic B cells in pemphigus vulgaris. Despite its great promise, current clinical CAR T-cell (or CAR-T) therapy carries a high risk of cytokine release syndrome, a potentially fatal systemic inflammatory response that can be manifest in cutaneous findings. For the dermatologist, the rapid clinical emergence of CAR-T therapy promises to treat and cure a variety of dermatological conditions, but it also requires an astute awareness of potential cutaneous complications in the increasing number of patients undergoing CAR-T therapy.
MeSH term(s)	Animals ; Antigens, CD19/immunology ; Cytokines/metabolism ; Dermatitis/etiology ; Humans ; Immunologic Techniques ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Lymphocyte Activation ; Lymphoma, B-Cell/immunology ; Lymphoma, B-Cell/therapy ; Melanoma/immunology ; Melanoma/therapy ; Postoperative Complications ; Receptors, Chimeric Antigen/genetics ; Signal Transduction ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes/physiology ; T-Lymphocytes/transplantation
Chemical Substances	Antigens, CD19 ; Cytokines ; Receptors, Chimeric Antigen
Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2018.09.002
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Article ; Online: Modeling Chronic Graft Versus Host Disease in Mice Using Allogeneic Bone Marrow and Splenocyte Transfer.

Schroeder, Mark A / Ashami, Kidist / Staser, Karl

Current protocols in pharmacology

2018 Volume 83, Issue 1, Page(s) e47

Abstract: This unit describes a method for allogeneic bone marrow and splenocyte transfer for the modeling of chronic graft versus host disease (cGVHD) in mice. Preclinical models provide clinically relevant platforms for mechanistic and therapeutic studies that ... ...

Abstract	This unit describes a method for allogeneic bone marrow and splenocyte transfer for the modeling of chronic graft versus host disease (cGVHD) in mice. Preclinical models provide clinically relevant platforms for mechanistic and therapeutic studies that may inform the treatment of patients suffering from cGVHD, a common and potentially severe complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Most murine models of cGVHD depend on the transfer of major histocompatibility complex (MHC)-mismatched bone marrow and whole splenocytes (or purified T cells) into an irradiated recipient. The bone marrow contains hematopoietic stem and progenitor cells necessary to reconstitute the irradiated host hematopoietic system, while splenocytes contain T cells that mediate cGVHD. Of note, specific mouse strains, splenocyte dose, bone marrow quantity, and irradiation doses vary widely across different cGVHD models. Here we describe donor bone marrow and splenocyte preparation, recipient irradiation and intravenous injection of donor cells, and clinical monitoring for disease emergence and progression. © 2018 by John Wiley & Sons, Inc.
MeSH term(s)	Animals ; Bone Marrow/immunology ; Bone Marrow/pathology ; Bone Marrow Transplantation/adverse effects ; Cells, Cultured ; Chronic Disease ; Disease Models, Animal ; Female ; Graft vs Host Disease/etiology ; Graft vs Host Disease/immunology ; Graft vs Host Disease/pathology ; Major Histocompatibility Complex ; Male ; Mice ; Mice, Inbred C57BL ; Spleen/cytology ; Spleen/immunology ; Spleen/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; T-Lymphocytes/transplantation ; Transplantation, Homologous
Language	English
Publishing date	2018-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1934-8290
ISSN (online)	1934-8290
DOI	10.1002/cpph.47
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Thesis ; Online: Erk1 and Erk2 in hematopoiesis, mast cell function, and the management of Nf1-associated leukemia and tumors

Staser, Karl W.

2012

Abstract: Neurofibromatosis type 1 is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene, which encodes a protein serving, at least in part, to accelerate the intrinsic hydrolysis of active Ras-GTP to ... ...

Abstract	Neurofibromatosis type 1 is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene, which encodes a protein serving, at least in part, to accelerate the intrinsic hydrolysis of active Ras-GTP to inactive Ras-GDP. A second-hit NF1 mutation precedes predominant NF1 neoplasms, including juvenile myelomoncytic leukemia (JMML) and plexiform neurofibroma formation, potentially fatal conditions with no medical therapy. While NF1 loss of heterozygosity (LOH) in myeloid progenitor cells sufficiently engenders leukemogenesis, plexiform neurofibroma formation depends on LOH in Schwann cells and Nf1 heterozygosity in the hematopoietic system. Specifically, recruited Nf1+/- mast cells accelerate tumorigenesis through secreted cytokines and growth factors. Nf1+/- mast cells depend upon deregulated signaling in c-kit pathways, a receptor system conserved in hematopoietic stem cells (HSCs). Accordingly, Nf1-/- myeloid progenitor cells, which can induce a JMML-like disease in mice, also demonstrate deregulated c-kit receptor signaling. C-kit-activated Nf1+/- mast cells and Nf1-/- myeloid progenitors both show increased latency and potency of active Erk1 and Erk2, the principal cytosolic-to-nuclear effectors of canonical Ras-Raf-Mek signaling. Thus, Erk represents a potential regulator of leukemogenesis and tumor-associated inflammation. However, single and combined Erk1 and Erk2 roles in HSC function, myelopoiesis, and mature mast cell physiology remain unknown, and recent hematopoietic studies relying on chemical Mek-Erk inhibitors have produced conflicting results. Here, we show that hematopoietic stability, myelopoiesis, and mast cell generation require Erk1 or Erk2, but individual isoforms are largely dispensable. Principally, Erk-disrupted hematopoietic stem cells incorporate BrdU but are incapable of dividing, a novel and cell type-specific Erk function. Similarly, mast cell proliferation requires Erk but cytokine production proceeds through other pathways, elucidating molecule-specific functions within the c-kit cascade. Based on these findings, we have reduced tumor mast cell infiltration by treating genetically-engineered tumor model mice with PD0325901, a preclinical Mek-Erk inhibitor. Moreover, we have devised a quadruple transgenic HSC transplantation model to examine dual Erk disruption in the context of Nf1 nullizygosity, testing whether diseased hematopoiesis requires Erk. These insights illuminate cell-specific Erk functions in normal and Nf1-deficient hematopoiesis, informing the feasibility of targeting Mek-Erk in NF1-associated disease.
Keywords	Molecular biology\|Cellular biology\|Biochemistry\|Medicine\|Oncology
Subject code	610
Language	ENG
Publishing date	2012-01-01 00:00:01.0
Publisher	Indiana University
Publishing country	us
Document type	Thesis ; Online
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Article ; Online: Baricitinib with cyclosporine eliminates acute graft rejection in fully mismatched skin and heart transplant models.

Abboud, Ramzi / Kim, Sena / Staser, Karl / Jayasinghe, Reyka G / Lim, Sora / Amatya, Parmeshwar / Frye, C Corbin / Kopecky, Benjamin / Ritchey, Julie / Gao, Feng / Lavine, Kory / Kreisel, Daniel / DiPersio, John F / Choi, Jaebok

Frontiers in immunology

2023 Volume 14, Page(s) 1264496

Abstract: Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have ... ...

Abstract	Solid organ transplant represents a potentially lifesaving procedure for patients suffering from end-stage heart, lung, liver, and kidney failure. However, rejection remains a significant source of morbidity and immunosuppressive medications have significant toxicities. Janus kinase (JAK) inhibitors are effective immunosuppressants in autoimmune diseases and graft versus host disease after allogeneic hematopoietic cell transplantation. Here we examine the role of JAK inhibition in preclinical fully major histocompatibility mismatched skin and heart allograft models. Baricitinib combined with cyclosporine A (CsA) preserved fully major histocompatibility mismatched skin grafts for the entirety of a 111-day experimental period. In baricitinib plus CsA treated mice, circulating CD4
MeSH term(s)	Humans ; Animals ; Mice ; Cyclosporine/therapeutic use ; Graft Rejection/prevention & control ; Heart Transplantation/adverse effects ; Sulfonamides
Chemical Substances	Cyclosporine (83HN0GTJ6D) ; baricitinib (ISP4442I3Y) ; Sulfonamides
Language	English
Publishing date	2023-09-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1264496
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Article ; Online: Histopathologic upgrading of nonmelanoma skin cancer at the time of Mohs micrographic surgery: A prospective review.

Kyllo, Rachel L / Staser, Karl W / Rosman, Ilana / Council, M Laurin / Hurst, Eva A

Journal of the American Academy of Dermatology

2019 Volume 81, Issue 2, Page(s) 541–547

Abstract: Background: Anecdotal experience and data from multiple retrospective studies have suggested that a significant percentage of nonmelanoma skin cancers (NMSCs) display an aggressive histologic subtype that is not diagnosed on initial biopsy.: Objective! ...

Abstract	Background: Anecdotal experience and data from multiple retrospective studies have suggested that a significant percentage of nonmelanoma skin cancers (NMSCs) display an aggressive histologic subtype that is not diagnosed on initial biopsy. Objective: To prospectively determine the proportion of NMSCs upgraded at the time of Mohs micrographic surgery (MMS) and examine the surgical parameters of upgraded lesions. Methods: In this prospective, cross-sectional study, all patients undergoing MMS for NMSC at our institution over the course of 1 year were screened for inclusion. Frozen sections were reviewed independently by 2 fellowship-trained Mohs surgeons. Results: In total, 265 of 2578 (10.3%) tumors displayed a more aggressive skin cancer histologic subtype on frozen-section analysis at the time of surgery than at the initial biopsy. Upgraded tumors required significantly more stages to reach tumor clearance, had a larger postoperative defect size, and more often required complicated repairs than nonupgraded tumors. Limitations: Single center study, limited time period, and cross-sectional design. Conclusion: A significant portion of MMS cases were upgraded at the time of surgery to a more aggressive subtype than that seen at the initial biopsy. Upgraded cases were larger and more surgically challenging than nonupgraded ones. This finding has important implications for primary dermatologists' referral practices and Mohs appropriate use criteria guidelines.
MeSH term(s)	Aged ; Aged, 80 and over ; Biopsy ; Carcinoma, Basal Cell/pathology ; Carcinoma, Basal Cell/surgery ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/surgery ; Cross-Sectional Studies ; Female ; Frozen Sections ; Humans ; Male ; Middle Aged ; Mohs Surgery ; Neoplasm Grading ; Prospective Studies ; Skin/pathology ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery
Language	English
Publishing date	2019-06-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	603641-7
ISSN	1097-6787 ; 0190-9622
ISSN (online)	1097-6787
ISSN	0190-9622
DOI	10.1016/j.jaad.2019.02.058
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Zs.A 1540: Show issues

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Article ; Online: The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia.

Schroeder, Mark A / Choi, Jaebok / Staser, Karl / DiPersio, John F

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

2017 Volume 24, Issue 6, Page(s) 1125–1134

Abstract: For patients with hematologic malignancies, allogeneic hematopoietic cell transplantation (alloHCT) offers a potential curative treatment option, primarily due to an allogeneic immune response against recipient tumor cells (ie, graft-versus-leukemia [GVL] ...

Abstract	For patients with hematologic malignancies, allogeneic hematopoietic cell transplantation (alloHCT) offers a potential curative treatment option, primarily due to an allogeneic immune response against recipient tumor cells (ie, graft-versus-leukemia [GVL] activity). However, many recipients of alloHCT develop graft-versus-host disease (GVHD), in which allogeneic immune responses lead to the damage of healthy tissue. GVHD is a leading cause of nonrelapse mortality and a key contributor to morbidity among patients undergoing alloHCT. Therefore, improving alloHCT outcomes will require treatment strategies that prevent or mitigate GVHD without disrupting GVL activity. Janus kinases (JAKs) are intracellular signaling molecules that are well positioned to regulate GVHD. A variety of cytokines that signal through the JAK signaling pathways play a role in regulating the development, proliferation, and activation of several immune cell types important for GVHD pathogenesis, including dendritic cells, macrophages, T cells, B cells, and neutrophils. Importantly, despite JAK regulation of GVHD, preclinical evidence suggests that JAK inhibition preserves GVL activity. Here we provide an overview of potential roles for JAK signaling in the pathogenesis of acute and chronic GVHD as well as effects on GVL activity. We also review preclinical and clinical results with JAK inhibitors in acute and chronic GVHD settings, with added focus on those actively being evaluated in patients with acute and chronic GVHD.
MeSH term(s)	Graft vs Host Disease/etiology ; Graft vs Leukemia Effect ; Hematopoietic Stem Cell Transplantation ; Humans ; Janus Kinases/physiology ; Signal Transduction/physiology ; Transplantation, Homologous
Chemical Substances	Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2017-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1474865-4
ISSN	1523-6536 ; 1083-8791
ISSN (online)	1523-6536
ISSN	1083-8791
DOI	10.1016/j.bbmt.2017.12.797
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Zs.A 5082: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: An "off-the-shelf" CD2 universal CAR-T therapy for T-cell malignancies.

Xiang, Jingyu / Devenport, Jessica M / Carter, Alun J / Staser, Karl W / Kim, Miriam Y / O' Neal, Julie / Ritchey, Julie K / Rettig, Michael P / Gao, Feng / Rettig, Garrett / Turk, Rolf / Lee, Byung Ha / Cooper, Matthew L / DiPersio, John F

Leukemia

2023 Volume 37, Issue 12, Page(s) 2448–2456

Abstract: T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic "universal" ... ...

Abstract	T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic "universal" CD2-targeting CAR-T cell (UCART2), in which the CD2 antigen is deleted to prevent fratricide, and the T-cell receptor is removed to prevent GvHD. UCART2 demonstrated efficacy against T-ALL and CTCL and prolonged the survival of tumor-engrafted NSG mice in vivo. To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). We also observed that UCART19ΔCD2 had reduced anti-tumor efficacy compared to UCART19 in a CD19+NALM6 xenograft model. Of note is that the reduced efficacy resulting from CD2 deletion was reversed when combined with rhIL-7-hyFc, a long-acting recombinant human interleukin-7. Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies.
MeSH term(s)	Humans ; Mice ; Animals ; T-Lymphocytes ; Receptors, Chimeric Antigen/genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Neoplasm Recurrence, Local ; Immunotherapy, Adoptive/methods ; Receptors, Antigen, T-Cell ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell ; Antigens, CD19
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02039-z
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