scholarly journals Adoptive T Cell Therapy for Epstein–Barr Virus Complications in Patients With Primary Immunodeficiency Disorders

2018 ◽  
Vol 9 ◽  
Author(s):  
Lauren P. McLaughlin ◽  
Catherine M. Bollard ◽  
Michael D. Keller
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Primary Immunodeficiency ◽  
Epstein Barr Virus ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Primary Immunodeficiency Disorders ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Phase I Clinical Trial of 4-1BB-based Adoptive T-Cell Therapy for Epstein-Barr Virus (EBV)-positive Tumors

2016 ◽  
Vol 39 (3) ◽  
pp. 140-148 ◽  
Author(s):  
Hyeon-Seok Eom ◽  
Beom K. Choi ◽  
Youngjoo Lee ◽  
Hyewon Lee ◽  
Tak Yun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Cell Therapy ◽  
Phase I ◽  
Epstein Barr Virus ◽  
Phase I Clinical Trial ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Barr Virus ◽  
Epstein Barr

Adoptive T-Cell Therapy for Epstein-Barr Virus-Positive Hodgkin’s Disease

2003 ◽  
Vol 110 (2-3) ◽  
pp. 149-153 ◽  
Author(s):  
M. Helen Huls ◽  
Cliona M. Rooney ◽  
Helen E. Heslop
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Adoptive T-Cell Therapy for Epstein-Barr Virus–Related Lymphomas

2021 ◽  
Vol 39 (5) ◽  
pp. 514-524
Author(s):  
Helen E. Heslop ◽  
Sandhya Sharma ◽  
Cliona M. Rooney
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Epstein Barr Virus ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Zara A. Ioannides ◽  
Peter A. Csurhes ◽  
Nanette L. Douglas ◽  
Gem Mackenroth ◽  
Andrew Swayne ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Cell Therapy ◽  
Clinical Improvement ◽  
Epstein Barr Virus ◽  
T Cell Therapy ◽  
Sustained Improvement ◽  
Barr Virus ◽  
Cell Immunity ◽  
Epstein Barr

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.Methods: We assessed participants 2 and 3 years after completion of T cell therapy.Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

scholarly journals Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinle Cui ◽  
Clifford M. Snapper
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Neutralizing Antibodies ◽  
Epstein Barr Virus ◽  
Immune Cell ◽  
Critical Role ◽  
Target Cells ◽  
T Cell Therapy ◽  
Barr Virus ◽  
Epstein Barr

Epstein-Barr virus (EBV) is the first human tumor virus discovered and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. Each year EBV associated cancers account for over 200,000 new cases of cancer and cause 150,000 deaths world-wide. EBV is also the primary cause of infectious mononucleosis, and up to 70% of adolescents and young adults in developed countries suffer from infectious mononucleosis. In addition, EBV has been shown to play a critical role in the pathogenesis of multiple sclerosis. An EBV prophylactic vaccine that induces neutralizing antibodies holds great promise for prevention of EBV associated diseases. EBV envelope proteins including gH/gL, gB and gp350 play key roles in EBV entry and infection of target cells, and neutralizing antibodies elicited by each of these proteins have shown to prevent EBV infection of target cells and markedly decrease EBV titers in the peripheral blood of humanized mice challenged with lethal dose EBV. Recent studies demonstrated that immunization with the combination of gH/gL, gB and/or gp350 induced markedly increased synergistic EBV neutralizing activity compared to immunization with individual proteins. As previous clinical trials focused on gp350 alone were partially successful, the inclusion of gH/gL and gB in a vaccine formulation with gp350 represents a promising approach of EBV prophylactic vaccine development. Therapeutic EBV vaccines have also been tested clinically with encouraging results. Immunization with various vaccine platforms expressing the EBV latent proteins EBNA1, LMP1, and/or LMP2 promoted specific CD4+ and CD8+ cytotoxic responses with anti-tumor activity. The addition of EBV envelope proteins gH/gL, gB and gp350 has the potential to increase the efficacy of a therapeutic EBV vaccine. The immune system plays a critical role in the control of tumors, and immune cell therapy has emerged as a promising treatment of cancers. Adoptive T-cell therapy has been successfully used in the prevention and treatment of post-transplant lymphoproliferative disorder. Chimeric antigen receptor T cell therapy and T cell receptor engineered T cell therapy targeting EBV latent proteins LMP1, LMP2 and/or EBNA1 have been in development, with the goal to increase the specificity and efficacy of treatment of EBV associated cancers.

scholarly journals Isolation of Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes That Lyse Reed-Sternberg Cells: Implications for Immune-Mediated Therapy of EBV+ Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 1978-1986 ◽  
Author(s):  
Amy P. Sing ◽  
Richard F. Ambinder ◽  
Doley J. Hong ◽  
Michael Jensen ◽  
Wendy Batten ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Barr Virus ◽  
Epstein Barr ◽  
T Cell Lines

Abstract A subset of Hodgkin's disease (HD) patients have detectable Epstein-Barr virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R-S cells express only a limited set of latent EBV proteins, but only LMP1 and LMP2 can potentially elicit a CD8+ cytotoxic T-lymphocyte (CTL) response. We have evaluated if either of these proteins could be used as targets for specific adoptive T-cell therapy for EBV-positive (EBV+) HD. The success of this strategy requires that R-S cells are susceptible to lysis by CD8+ CTL, and that CTL specific for LMP1 and LMP2 can be detected and potentially amplified in HD patients. Antigen presentation and CTL sensitivity was evaluated with an in vitro maintained, phenotypically representative R-S cell line, HDLM-2. The R-S cells were able to process and present viral proteins, and to be efficiently lysed by specific CTL in a Class I–restricted manner. Since CTL responses to LMP1 and LMP2 do not represent the dominant responses to EBV, we examined if CTL clones specific for these proteins could be isolated despite the presence of weak or nondetectable responses in polyclonal T-cell lines. LMP-specific clones were generated from individuals either by cloning from the polyclonal EBV-reactive T-cell lines or by direct stimulation of peripheral blood mononuclear cells (PBMC) with cells expressing LMP1 or LMP2 as the only EBV protein. Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV+ tumors.

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