chimeric t cell and lymphoma | Page 2

Florian Huemer, Michael Leisch, Roland Geisberger, Thomas Melchardt, Gabriel Rinnerthaler, Nadja Zaborsky, Richard Greil
The therapeutic concept of unleashing a pre-existing immune response against the tumor by the application of immune-checkpoint inhibitors (ICI) has resulted in long-term survival in advanced cancer patient subgroups. However, the majority of patients do not benefit from single-agent ICI and therefore new combination strategies are eagerly necessitated. In addition to conventional chemotherapy, kinase inhibitors as well as tumor-specific vaccinations are extensively investigated in combination with ICI to augment therapy responses...
April 19, 2020: International Journal of Molecular Sciences
Wenqun Zhang, Jing Yang, Chunju Zhou, Bo Hu, Ling Jin, Biping Deng, Yang Liu, Shan Wang, Alex H Chang, Juan Du, Zifen Gao, Yonghong Zhang
No abstract text is available yet for this article.
April 22, 2020: Blood
Shu Zhou, Weiming Li, Yi Xiao, Xiaoying Zhu, Zhaodong Zhong, Qing Li, Fanjun Cheng, Ping Zou, Yong You, Xiaojian Zhu
Chimeric antigen receptor (CAR) T-cell immunotherapy is rapidly emerging as a promising novel treatment for malignancies. To broaden the success of CAR T-cell treatment for chronic myeloid leukaemia (CML), we attempted to construct a CD26 CAR T-cell product to target tyrosine kinase inhibitor-insensitive leukaemia stem cells (LSCs), which have been a challenge to cure for several decades and can be discriminated from healthy stem cells by the robust biomarker CD26. Of additional interest is that CD26 has also been reported to be a multi-purpose therapeutic target for other malignancies...
April 21, 2020: Leukemia
Feng Zhu, Guoqing Wei, Mingming Zhang, Houli Zhao, Wenjun Wu, Luxin Yang, Yongxian Hu, He Huang
BACKGROUND: Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. CAR-T therapy has been extensively applied in the clinical setting; however, few systematic studies have evaluated the cost of CAR-T treatment. This study was conducted to evaluate the total cost and cost structure of CAR-T therapy and identify potential risk factors leading to increased costs. METHODS: We identified the associated risk factors in 89 patients in a phase 1/2 study...
January 2020: Cell Transplantation
Tongjuan Li, Jiaqi Tan, Liting Chen, Dong Kuang, Xia Mao, Yaoyao Lou, Jianfeng Zhou, Xiaoxi Zhou
RATIONALE: B cell lymphoma can co-occur with multiple myeloma (MM), and the prognosis in this case is usually poor. We propose the combination of CD19-chimeric antigen receptor (CAR) T cells and BCMA-CAR T cells for the treatment of such patients to obtain a superior prognosis. PATIENT CONCERNS: We present a 50-year-old patient with previous B cell lymphoma and subsequent multiple myeloma (MM). DIAGNOSIS: A diagnosis of B cell lymphoma and MM was made...
April 2020: Medicine (Baltimore)
Mohamad Mohty, Remy Dulery, Jordan Gauthier, Florent Malard, Eolia Brissot, Mahmoud Aljurf, Ali Bazarbachi, Christian Chabanon, Mohamed A Kharfan-Dabaja, Bipin N Savani, He Huang, Saad S Kenderian, Miguel-Angel Perales, Ibrahim Yakoub-Agha, Arnon Nagler
The goal of this review is to firstly address the concept of chimeric antigen receptor T-cell (CAR T-cell) therapy and where it fits in the evolving landscape of the management of patients with refractory/relapsed diffuse large B-cell lymphoma. The recognition of the indications for CAR T-cell therapy for patients with aggressive B-cell lymphoma will be discussed, including a review of the algorithms and selection criteria for CAR T-cell therapy and finally, the role of bridging therapy and the timing of CAR T-cell therapy in augmenting chances of a successful outcome...
April 18, 2020: Bone Marrow Transplantation
Jun-Xia Cao, Hui Wang, Wei-Jian Gao, Jia You, Li-Hua Wu, Zheng-Xu Wang
Our objective was to summarize the side effect of chimeric antigen receptor (CAR)-T cell therapy in patients with acute lymphocytic leukemia (ALL) and lymphoma. Two independent reviewers extracted relevant data. A total of 35 hematologic malignancy studies with CD19 CAR-T cell were included (1412 participants). Severe cytokine release syndrome (sCRS) proportion was experienced by 18.5% (95% confidence interval [CI], 0.128-0.259; P = 0.000) of 982 patients with the National Cancer Institute/Lee/common terminology criteria for adverse events grading system...
April 2020: Cytotherapy
Stella Bouziana, Dimitrios Bouzianas
Patients with refractory or relapsed (R/R) B-acute lymphoblastic leukemia (B-ALL) and highly aggressive B-non-Hodgkin lymphoma (B-NHL) have very dismal prognosis and limited treatment options. The advent of chimeric antigen receptor (CAR) T-cells constitutes a milestone in current cell and gene therapies, covering the unmet need of treatment of high-risk patients and bringing immunotherapies one step closer towards cancer therapeutics, including hematological malignancies. CAR T-cells targeting CD19 antigen have shown startling remission rates in heavily pre-treated B-ALL and B-NHL patients, in whom CAR T-cell therapy may sometimes be their last treatment resort...
April 15, 2020: Biology of Blood and Marrow Transplantation
(no author information available yet)
KTE-X19, an investigational chimeric antigen receptor T-cell therapy, has shown promising efficacy in patients with relapsed/refractory mantle cell lymphoma. Based on data from the ZUMA-2 trial, it is now under the FDA's priority review and could soon be a new standard of care for this rare hematologic malignancy.
April 17, 2020: Cancer Discovery
Ranjit Nair, Jason Westin
CAR-T (chimeric antigens receptor-T) cell therapy is a breakthrough therapy of the twenty-first century for the management of different malignancies including lymphomas and leukemias. Numeral trials are underway to understand the optimal CAR-T cell design and dose to maximize efficacy and mitigate toxicity. Currently two CAR-T cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, are approved by the US Food and Drug Administration, which have shown excellent responses in otherwise poor prognostic lymphomas and leukemias...
2020: Advances in Experimental Medicine and Biology
Meijun Zheng, Lingyu Yu, Juanjuan Hu, Zongliang Zhang, Haiyang Wang, Dan Lu, Xin Tang, Jianhan Huang, Kunhong Zhong, Zeng Wang, Yisong Li, Gang Guo, Shixi Liu, Aiping Tong, Hui Yang
Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines...
April 13, 2020: Translational Oncology
Veronika Bachanova, Michael R Bishop, Parastoo Dahi, Bhagirathbhai Dholaria, Stephan A Grupp, Brandon Hayes-Lattin, Murali Janakiram, Richard T Maziarz, Joseph P McGuirk, Loretta J Nastoupil, Olalekan O Oluwole, Miguel-Angel Perales, David L Porter, Peter A Riedell
The COVID-19 pandemic has significantly impacted the delivery of cellular therapeutics, including chimeric antigen receptor (CAR) T cells. This impact has extended beyond patient care to include logistics, administration, and distribution of increasingly limited health care resources. Based on the collective experience of the CAR T-cell Consortium investigators, we review and address several questions and concerns regarding cellular therapy administration in the setting of COVID-19 and make general recommendations to address these issues...
April 13, 2020: Biology of Blood and Marrow Transplantation
Li Wang, Wei Qin, Yu-Jia Huo, Xiao Li, Qing Shi, John E J Rasko, Anne Janin, Wei-Li Zhao
The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment...
March 6, 2020: Signal Transduction and Targeted Therapy
Keyvan Fallah-Mehrjardi, Hamid Reza Mirzaei, Elham Masoumi, Leila Jafarzadeh, Hosein Rostamian, Mohammad Khakpoor-Koosheh, Khadijeh Alishah, Farshid Noorbakhsh, Jamshid Hadjati
In spite of impressive results in the treatment of acute lymphoblastic B cell leukemia (B-ALL) with chimeric antigen receptor (CAR) T cells, the clinical outcome of some hematological cancers like follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) has not been very promising likely due to immunosuppressive networks within tumor microenvironment. Hypoxia in the microenvironment of hematological malignancies and consequently generation of adenosine molecule is appeared to be correlated with immunosuppression, tumor progression, and relapse...
April 11, 2020: Immunology Letters
Roch Houot, Philippe Armand, Caron A Jacobson
No abstract text is available yet for this article.
May 2020: European Journal of Cancer
Adrian H J Tan, Natasha Vinanica, Dario Campana
Infusion of T lymphocytes expressing chimeric antigen receptors (CARs) can produce extraordinary antitumor activity in patients with leukemia, lymphoma, and myeloma. The signaling mechanisms activating T cells and provoking tumor cell killing also trigger cytokine secretion and macrophage activation, leading to cytokine release syndrome (CRS). CRS is a serious side effect of CAR-T cells, and proinflammatory interleukin-6 (IL-6) is central to its pathogenesis. To endow T cells with anti-CRS activity, we designed a nonsignaling membrane-bound IL-6 receptor (mbaIL6) constituted by a single chain variable fragment derived from an anti-IL-6 antibody linked to a transmembrane anchoring peptide...
April 14, 2020: Blood Advances
Stephen J Schuster, Richard T Maziarz, Elisha S Rusch, Junlong Li, James E Signorovitch, Vadim V Romanov, Frederick L Locke, David G Maloney
Chimeric antigen receptor T-cell (CAR-T) therapy yields durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Cytokine release syndrome (CRS) is a CAR-T therapy-related adverse event. To date, clinical trials of different CAR-T products have not been aligned on CRS grading scales and management algorithms. We assessed concordance between the Penn, Lee, and American Society for Transplantation and Cellular Therapy (ASTCT) grading systems by retrospectively regrading CRS events in the JULIET (A Phase 2, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory DLBCL) trial...
April 14, 2020: Blood Advances
Richard T Maziarz, Stephen J Schuster, Vadim V Romanov, Elisha S Rusch, Junlong Li, James E Signorovitch, David G Maloney, Frederick L Locke
Chimeric antigen receptor-T (CAR-T) cell therapy achieves durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), but may be associated with neurological toxicity (NT). We retrospectively assessed differences and concordance among 3 available grading scales (the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 [CTCAE], modified CAR-T Related Encephalopathy Syndrome [mCRES], and American Society for Transplantation and Cellular Therapy [ASTCT] scales) applied to the same set of NT data from the JULIET (A Phase 2, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory DLBCL) trial...
April 14, 2020: Blood Advances
Shinji Yamada, Mika K Kaneko, Yusuke Sayama, Teizo Asano, Masato Sano, Miyuki Yanaka, Takuro Nakamura, Saki Okamoto, Saori Handa, Yu Komatsu, Yoshimi Nakamura, Yoshikazu Furusawa, Junko Takei, Yukinari Kato
CD19 is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is expressed in normal and neoplastic B cells, and it modulates the threshold of B cell activation for amplifying B cell receptor signaling. Blinatumomab (a CD3-CD19-bispecific T cell-engaging antibody) and tisagenlecleucel (genetically modified T cells that express a CD19 chimeric antigen receptor [CART-19]) provide significant benefits for patients with CD19-positive relapsed or refractory B cell malignancies. In this study, we first employed the Cell-Based Immunization and Screening (CBIS) method to produce anti-CD19 monoclonal antibodies using CD19-overexpressing cells for both immunization and screening...
April 2020: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Andreas A Hombach, Ulf Geumann, Christine Günther, Felix G Hermann, Hinrich Abken
Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-γ and TNF-α, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death...
April 3, 2020: Cells
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