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Article ; Online: Impact of tocilizumab on anti-CD19 chimeric antigen receptor T-cell therapy in B-cell acute lymphoblastic leukemia.

Wang, Xiangmin / Zhang, Bingpei / Zhang, Qing / Zhou, Hongyuan / Sun, Qian / Zhou, Yi / Li, Tianci / Zhou, Dian / Shen, Ziyuan / Zhang, Jiaoli / Li, Ping / Liang, Aibin / Zhou, Keshu / Han, Lu / Hu, Yongxian / Yang, Yun / Cao, Jiang / Li, Zhenyu / Xu, Kailin /

Sang, Wei

Cancer

2024

Abstract: Background: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T ... whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective ... of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy.: Methods ...

Abstract	Background: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy. Methods: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. Results: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. Conclusions: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35316
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Article ; Online: Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

Faramand, Rawan G / Lee, Sae Bom / Jain, Michael D / Cao, Biwei / Wang, Xuefeng / Rejeski, Kai / Subklewe, Marion / Fahrmann, Johannes F / Saini, Neeraj Y / Hanash, Samir M / Kang, Yun Pyo / Chang, Darwin / Rodriguez, Paolo C / Dean, Erin A / Nishihori, Taiga / Shah, Bijal D / Lazaryan, Aleksandr / Chavez, Julio / Khimani, Farhad /

Pinilla-Ibarz, Javier A / Dam, Marian / Reid, Kayla M / Corallo, Salvatore A / Menges, Meghan / Hidalgo Vargas, Melanie / Mandula, Jay K / Holliday, Brian A / Bachmeier, Christina A / Speth, Kelly / Song, Qinghua / Mattie, Mike / Locke, Frederick L / Davila, Marco L

Blood cancer discovery

2024 Volume 5, Issue 2, Page(s) 106–113

Abstract: A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric ... antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe ... chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy ...

Abstract	A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy. Significance: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/therapeutic use ; Lymphoma, Large B-Cell, Diffuse/therapy ; Adaptor Proteins, Signal Transducing ; Antigens, CD19/therapeutic use ; Blood Proteins ; C-Reactive Protein ; Ferritins ; Hematologic Neoplasms
Chemical Substances	Receptors, Chimeric Antigen ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Blood Proteins ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2)
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028898-8
ISSN	2643-3249 ; 2643-3230
ISSN (online)	2643-3249
ISSN	2643-3230
DOI	10.1158/2643-3230.BCD-23-0056
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Article ; Online: Prophylactic donor-derived CD19 CAR-T cell infusion for preventing relapse in high-risk B-ALL after allogeneic hematopoietic stem cell transplantation.

Lu, Wenyi / Lyu, Hairong / Xiao, Xia / Bai, Xue / Zhang, Meng / Wang, Jiaxi / Pu, Yedi / Meng, Juanxia / Zhang, Xiaomei / Zhu, Haibo / Yuan, Ting / Wang, Bing / Jin, Xin / Cao, Xinping / Wang, Zhao / Xie, Tianle / Meng, Haotian / Stepanov, Alexey V / Gabibov, Alexander G /

An, Yuxin / Sun, Rui / Zhang, Yu / Maschan, Mikhail A / Zhu, Zunmin / Zhang, Hongkai / Zhao, Mingfeng

Leukemia

2024

Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-024-02251-5
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Article ; Online: A CAR-T response prediction model for r/r B-NHL patients based on a T cell subset nomogram.

Zhang, Xiaomei / Sun, Rui / Zhang, Meng / Zhao, Yifan / Cao, Xinping / Guo, Ruiting / Zhang, Yi / Liu, Xingzhong / Lyu, Cuicui / Zhao, Mingfeng

Cancer immunology, immunotherapy : CII

2024 Volume 73, Issue 2, Page(s) 33

Abstract: Background: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B cell no ... influencing factors of the efficacy of CD19 CAR-T cell infusion in the treatment of r/r B-NHL and to establish ... in cytotoxic T cells (Tc) was an independent risk factor for response to CD19 CAR-T cell therapy in r/r B-NHL ...

Abstract	Background: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B cell no-Hodgkin lymphoma (NHL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here investigate the independent influencing factors of the efficacy of CD19 CAR-T cell infusion in the treatment of r/r B-NHL and to establish an early prediction model. Methods: A total of 43 r/r B-NHL patients were enrolled in this retrospective study. The patients' general data were recorded, and the primary endpoint is the patients' treatment response. The independent factors of complete remission (CR) and partial remission (PR) were investigated by univariate and binary logistic regression analysis, and the prediction model of the probability of CR was constructed according to the determined independent factors. Receiver operating characteristic (ROC) and calibration plot were used to assess the discrimination and calibration of the established model. Furthermore, we collected 15 participators to validate the model. Results: Univariate analysis and binary logistic regression analysis of 43 patients showed that the ratio of central memory T cell (Tcm) and naïve T cell (Tn) in cytotoxic T cells (Tc) was an independent risk factor for response to CD19 CAR-T cell therapy in r/r B-NHL. On this basis, the area under the curve (AUC) of Tcm in the Tc and Tn in the Tc nomogram model was 0.914 (95%CI 0.832-0.996), the sensitivity was 83%, and the specificity was 74.2%, which had excellent predictive value. We did not found the difference of the progression-free survival (PFS). Conclusions: The ratio of Tcm and Tn in Tc was found to be able to predict the treatment response of CD19 CAR-T cells in r/r B-NHL. We have established a nomogram model for the assessment of the CD19 CAR-T therapy response presented high specificity and sensitivity.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Nomograms ; Retrospective Studies ; Immunotherapy, Adoptive ; T-Lymphocyte Subsets ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Antigens, CD19
Language	English
Publishing date	2024-01-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-023-03618-w
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Zs.A 1237: Show issues

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Article ; Online: Allogeneic CAR-T cells with of HLA-A/B and TRAC disruption exhibit promising antitumor capacity against B cell malignancies.

Chen, Xinfeng / Tan, Binghe / Xing, Haizhou / Zhao, Xuan / Ping, Yu / Zhang, Zhen / Huang, Jianmin / Shi, Xiujuan / Zhang, Na / Lin, Boxu / Cao, Weijie / Li, Xin / Zhang, Xudong / Li, Ling / Jiang, Zhongxing / Zhang, Mingzhi / Li, Wei / Liu, Mingyao / Du, Bing /

Zhang, Yi

Cancer immunology, immunotherapy : CII

2024 Volume 73, Issue 1, Page(s) 13

Abstract: Background: Although chimeric antigen receptor T (CAR-T) cells have been proven to be an effective ... way of treating B cell malignancies, a lot of patients could not benefit from it because of failure ... in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore ...

Abstract	Background: Although chimeric antigen receptor T (CAR-T) cells have been proven to be an effective way of treating B cell malignancies, a lot of patients could not benefit from it because of failure in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore universal CAR-T cell products to extend the clinical accessibility. Methods: The antitumor activity of CRISPR/Cas9-edited allogeneic anti-CD19 CAR-T (CAR-T19) cells was assessed in vitro, in animal models, and in patients with relapsed/refractory (R/R) acute B cell lymphoblastic leukemia (B-ALL) or diffuse large B cell lymphoma. Results: B2M Conclusions: The nU-CAR-T19 cells showed a strong response in R/R B-ALL. nU-CAR-T19 cells have the potential to be a promising new approach for treating R/R B cell malignancies.
MeSH term(s)	Animals ; Humans ; Receptors, Chimeric Antigen/genetics ; Antibodies ; Antigens, CD19 ; Graft vs Host Disease ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell ; Hematopoietic Stem Cell Transplantation ; T-Lymphocytes ; HLA-A Antigens
Chemical Substances	Receptors, Chimeric Antigen ; Antibodies ; Antigens, CD19 ; HLA-A Antigens
Language	English
Publishing date	2024-01-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-023-03586-1
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Article ; Online: Murine regulatory T cells utilize granzyme B to promote tumor metastasis.

Tibbs, Ellis / Kandy, Rakhee Rathnam Kalari / Jiao, Delong / Wu, Long / Cao, Xuefang

Cancer immunology, immunotherapy : CII

2023 Volume 72, Issue 9, Page(s) 2927–2937

Abstract: Regulatory T cells (Tregs) possess a wide range of mechanisms for immune suppression ... Among them, Granzyme B (GzmB) and perforin expressed by Tregs were shown to inhibit tumor clearance in previous reports ... which contradicted the canonical roles of these cytotoxic molecules expressed by cytotoxic T cells and NK cells ...

Abstract	Regulatory T cells (Tregs) possess a wide range of mechanisms for immune suppression. Among them, Granzyme B (GzmB) and perforin expressed by Tregs were shown to inhibit tumor clearance in previous reports, which contradicted the canonical roles of these cytotoxic molecules expressed by cytotoxic T cells and NK cells in antitumor immune responses. Given the ability of the tumor to manipulate the microenvironment, Treg-derived GzmB function may represent an important approach to aid in tumor growth as well as facilitating tumor metastasis. In this study, we utilized Treg-specific GzmB knockout (Foxp3
MeSH term(s)	Mice ; Animals ; T-Lymphocytes, Regulatory ; Granzymes/metabolism ; T-Lymphocytes, Cytotoxic ; Lung/pathology ; CD8-Positive T-Lymphocytes/metabolism
Chemical Substances	Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2023-02-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-023-03410-w
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Article ; Online: Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.

Chu, Fuliang / Cao, Jingjing / Liu, Jingwei / Yang, Haopeng / Davis, Timothy J / Kuang, Shao-Qing / Cheng, Xiaoyun / Zhang, Zheng / Karri, Swathi / Vien, Long T / Bover, Laura / Sun, Ryan / Vega, Francisco / Green, Michael / Davis, Richard Eric / Neelapu, Sattva S

Journal for immunotherapy of cancer

2023 Volume 11, Issue 11

Abstract: ... Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen ... Background: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable ... effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance ...

Abstract	Background: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas. Methods: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models. Results: We found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19 Conclusion: Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen ; Neoplasm Recurrence, Local/drug therapy ; Lymphoma, B-Cell/drug therapy ; T-Lymphocytes ; Antibodies, Monoclonal/metabolism
Chemical Substances	Receptors, Chimeric Antigen ; Antibodies, Monoclonal
Language	English
Publishing date	2023-11-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-007515
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Article: [Characteristics and impact factors of SARS-CoV-2 infection in adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma receiving chimeric antigen receptor T-cell therapy].

Ge, T / Liu, H / Wang, Z H / Cao, Y / Zhang, Y C / Huang, L / Qian, W B / Zhou, X X

Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

2023 Volume 44, Issue 10, Page(s) 825–831

Abstract: Objective: ...

Abstract	Objective:
MeSH term(s)	Humans ; Adult ; Middle Aged ; Receptors, Chimeric Antigen ; Retrospective Studies ; COVID-19/therapy ; SARS-CoV-2 ; Lymphoma, B-Cell/therapy ; Cell- and Tissue-Based Therapy
Chemical Substances	Receptors, Chimeric Antigen
Language	Chinese
Publishing date	2023-11-15
Publishing country	China
Document type	English Abstract ; Journal Article
ZDB-ID	2997162-7
ISSN	0253-2727 ; 0253-2727
ISSN (online)	0253-2727
ISSN	0253-2727
DOI	10.3760/cma.j.issn.0253-2727.2023.10.006
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Article ; Online: A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice.

Song, Yang / Hu, Hongqiao / Xiao, Kang / Huang, Xinghu / Guo, Hong / Shi, Yuqing / Zhao, Jiannan / Zhu, Shuangli / Ji, Tianjiao / Xia, Baicheng / Jiang, Jie / Cao, Lei / Zhang, Yong / Zhang, Yan / Xu, Wenbo

Microbiology spectrum

2023 , Page(s) e0419422

Abstract: ... this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T ...

Abstract	Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developing the capacity for immune evasion and resistance to existing vaccines and drugs. To address this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T cell immunity, and rapid production. Synthetic peptide vaccines, which are inexpensive and quick to produce, show low toxicity, and can be selected from the conserved SARS-CoV-2 proteome, are promising candidates. In this study, we evaluated the effectiveness of a synthetic peptide cocktail containing three murine CD4
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04194-22
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Article: Composite diffuse large B-cell lymphoma and peripheral T-cell lymphoma: a case report with two-year follow-up and literature review.

Gu, Jiwei / Qian, Juan / Cao, Xin

Frontiers in oncology

2024 Volume 14, Page(s) 1272209

Abstract: ... diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS ...

Abstract	Composite lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in the same organ are rare. Here, we report a case of a 75-year-old male patient admitted to our emergency department with intestinal obstruction presenting with abdominal pain and vomiting. He underwent partial resection of the small intestine under general anesthesia, and subsequent histopathology confirmed the mass to be composite DLBCL and PTCL-NOS. The patient received chemotherapy with a rituximab-based regimen and achieved complete remission (CR). However, the recurrent disease presented with obstruction again ten months after treatment. He refused a second surgery, but salvage treatment was not effective. The patient survived for 20 months after diagnosis. In addition, we did a literature review to understand the clinical features, pathology, treatment, and prognosis of this type of composite lymphoma.
Language	English
Publishing date	2024-03-11
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2024.1272209
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