An Open Single-center, Phase I Proof of Concept Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy With Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients With a First Clinical Episode Highly Suggestive of Multiple Sclerosis

The etiologic mechanisms involved in multiple sclerosis (MS) are not yet fully understood. Indeed MS is a multifactorial disease involving genetic and environmental factors and Epstein-Barr-Virus (EBV) could be one of these factors. However the link between EBV infection and the immunological mechanisms underlying MS is not clear. Robust sero-epidemiological evidences support an association between EBV infection and MS, and immunological data suggest an altered/deficient immune response against this virus. In healthy individuals EBV produces a persistent infection that is tightly controlled by the immune system. In patients with MS, cellular and humoral immune studies demonstrate an altered response against the virus with a T-cell abnormal reactivity against the EBV-infected autologous B-cells, elevated humoral immune response to Epstein Barr Nuclear Antigen-1, and in the case of children, an increased EBV shedding, demonstrating frequent EBV reactivations. Thus, it has been proposed, that patients with MS present a partially inefficient control of the EBV infection. Some experimental data support the hypothesis suggesting that the presence of autoreactive EBV-B cells in the meninges of patients, probably due to an insufficient clearance of these cells by the immune system, lead to the infiltration of autoreactive T cells. Another hypothesis also suggests a deficient control of the virus, in that case during the inactive phase of the disease. Together, the above data and hypotheses lead to the notion that an immune intervention capable of restoring the host-EBV balance could be beneficial to MS patients In this project, we will assess the feasibility and safety of autologous transfer of several amounts of CD8 T cells directed against autologous EBV transformed B cell lines, in order to finally restore an efficient control of EBV in MS patients. The main objective of the project is to test the feasibility and safety of the process, while efficacy parameters will be also assessed in secondary objectives.

Start Date26 Jan 2021

Sponsor / Collaborator

Nantes University Hospital

NCT00953420 / CompletedPhase 2IIT

Phase II Study of Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes in Patients With Refractory/Relapsed EBV-positive Nasopharyngeal Carcinoma(CADEN)

Patients have a type of cancer called nasopharyngeal carcinoma (NPC) that has either come back or not gone away after the best known standard treatments.
Most patients that respond to chemotherapy once their NPC tumors have come back have been treated with a platinum-based medication like cisplatin. However, since many patients are given cisplatin during their initial treatment for NPC, in this study, they will be treated with another platinum-based chemotherapy medicine that has been used in patients with NPC called carboplatin. In this study, carboplatin will be used in combination with another drug called docetaxel. Other studies in patients with advanced head and neck cancer have shown that docetaxel can cause tumors to respond better and allow patients to survive longer when added to the standard treatments for those diseases.
Some patients with NPC show evidence of infection with the virus that causes infectious mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage disease, suggesting that it may play a role in causing NPC. Previously, patients have been treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the laboratory and taught to recognize and attack EBV infected cells. In the past, patients were either given the cells alone or just after they had received a medication to briefly lower their white blood cell count. In both cases, many patients had their tumors shrink and in some cases completely disappear after being treated with these EBV-specific cytotoxic T cells.
Investigators have now decided to look at how patients with NPC and their tumors respond to the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to participate in this study since the NPC tumor is associated with EBV and has either come back or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an investigational treatment not approved by the Food and Drug Administration.
The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors respond when treated with carboplatin and docetaxel followed by EBV-CTL.

Start Date01 Nov 2009

Sponsor / Collaborator

Baylor College of Medicine

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100 Clinical Results associated with Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

100 Translational Medicine associated with Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

100 Patents (Medical) associated with Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

Literatures (Medical) associated with Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

01 Nov 2023·iScience

Advances and challenges of immunotherapies in NK/T cell lymphomas

Review

Author: He, Ling ; Dai, Lei ; Peng, Xingchen ; Chen, Na

Natural killer (NK)/T cell lymphoma (NKTCL) is a rare subtype of Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma characterized by poor clinical outcomes. It is more common in East Asian and Latin American countries. Despite the introduction of asparaginase/pegaspargase-based chemotherapy, the prognosis of patients with advanced NKTCL needs to be improved, and few salvage treatment options are available for relapsed/refractory patients who fail chemotherapy. Although many unknowns remain, novel treatment strategies to further improve outcomes are urgently needed. Immunotherapy has emerged and shown favorable antitumor activity in NKTCL, including monoclonal antibodies targeting immune checkpoint inhibitors, other receptors on the cellular membrane, and cellular immunotherapy, which could enhance immune cells attack on tumor cells. In this review, we provide an overview of recent immunotherapy in NKTCL, focusing on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), chimeric antigen receptor (CAR) T cells, EBV-specific cytotoxic T lymphocytes, immunomodulatory agents, and other targeted agents, as well as the current progress and challenges in the field.

03 May 2016·OncoImmunologyQ2 · MEDICINE

Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation

Q2 · MEDICINE

ArticleOA

Author: Liang, Xinquan ; Wu, Meiqing ; Jiang, Xinmiao ; Song, Chaoyang ; Xu, Lanping ; Xu, Na ; Xuan, Li ; Zhou, Hongsheng ; Zhang, Yu ; Huang, Xiaojun ; Dai, Min ; Jiang, Qianli ; Liu, Can ; Sun, Jin ; Liu, Daihong ; Huang, Fen ; Liu, Qifa ; Fan, Zhiping

To improve prognosis of post-transplant lymphoproliferative disease (PTLD), a sequential therapeutic strategy that rituximab-based treatments followed by donor lymphocyte infusion (DLI) or autologous EBV-specific cytotoxic T lymphocytes (EBV-CTL) for biopsy-proven EBV-associated PTLD in recipients of allogeneic hematopoietic stem cell transplantation was designed. 84 patients with EBV-PTLD were enrolled in this prospective study. After two cycles of the rituximab-based treatments, 68 of 84 patients (81% [95% CI 71-88]) responded and 52 (62% [51-72]) had CRs. This increased to 73 of 77 patients (95% [87-98]) with completion of sequential cell infusions, and 70 of 77 (91% [82-96]) achieved CRs after DLI or autologous EBV-CTL infusion. 22 patients experienced acute GVHD (aGVHD) (grade I in 5 and grade II in 13, grade III in 4) and 13 chronic GVHD (limited cGVHD in 7 and extensive cGVHD in 6) in 62 patients undergoing a median of three doses of DLI. The incidences of GVHD were similar between DLI and EBV-CTL group (aGVHD 35% vs. 33%, p = 0.876; cGVHD 21% vs. 13%; p = 0.503). EBV-CTL activity after the rituximab-based treatments did not change, while increased after cell infusions and reached its maximum in the 3rd or 6th month after EBV-CTL or DLI treatment, respectively. The 5-y cumulative incidence of PTLD relapse was 4.5% ± 3.3%. The 5-y overall survival (OS) and progression-free survival (PFS) after PTLD were 70.7% ± 5.2% and 68.9% ± 5.3%, respectively. Rituximab-based treatments combined with adoptive cellular immunotherapy might elevate CR rates and reduce relapse of PTLD after allo-HSCT.

100 Deals associated with Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


VANCE (ESMO2022)	Phase 3	Advanced Nasopharyngeal Carcinoma First line	330	Gemcitabine and carboplatin (GC) followed by Epstein Barr virus-specific autologous cytotoxic T lymphocytes (EBV-CTL)	(gqjbczdrmh) = ugkkceusou qprrxyfytz (otcmdboavi, 19.7 - 31.8)	Negative	12 Sep 2022
VANCE (ESMO2022)	Phase 3	Advanced Nasopharyngeal Carcinoma First line	330	GC alone	(gqjbczdrmh) = wkkgfsuqvk qprrxyfytz (otcmdboavi, 19.7 - 32.8)	Negative	12 Sep 2022
ASCO2010	Not Applicable	Carcinoma	27	EBV-specific cytotoxic T-lymphocytes	rqawnfamyv(rknviunkto) = efengegcxl umwnvkvjrl (vvzknxjnvc ) View more	-	20 May 2010

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Autologous EBV-specific Cytotoxic T Lymphocytes(Nantes University Hospital)

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