A novel Epstein–Barr virus-latent membrane protein-1-specific T-cell receptor for TCR gene therapy

Cho, Hyun-Il; Kim, Un-Hee; Shin, A-Ri; Won, Joong-Sun; Lee, Hyun-Joo; Sohn, Honglae; Kim, Tai‐Gyu

doi:10.1038/bjc.2017.475

Cited by 38 publications

(32 citation statements)

References 58 publications

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“…This antibody, formulated as a T cell engager with an additional specificity for CD3, was able to redirect adoptively transferred T cells towards LCL elimination in immune compromised mice. Moreover, LMP1-specific HLA-A2 restricted TCRs confer efficient T cell recognition of EBV-associated tumor cells in vitro [56]. These studies confirm that CD8 + T cell responses against LMP1 and LMP2 are efficient in targeting EBV-associated lymphomas, as has also been observed in the clinic [57].…”

Section: Characteristics Of Cell-mediated Immune Control Against Ebv supporting

confidence: 76%

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Münz

2019

Vaccines

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Mice with reconstituted human immune system components (humanized mice) offer the unique opportunity to test vaccines preclinically in the context of vaccine adjuvant sensing by human antigen presenting cells and priming of human cytotoxic lymphocyte populations. These features are particularly attractive for immune control of the Epstein–Barr virus (EBV), which represents the most potent growth-transforming pathogen in man and exclusively relies on cytotoxic lymphocytes for its asymptomatic persistence in the vast majority of healthy virus carriers. This immune control is particularly impressive because EBV infects more than 95% of the human adult population and persists without pathology for more than 50 years in most of them. This review will discuss the pathologies that EBV elicits in humanized mice, which immune responses control it in this model, as well as which passive and active vaccination schemes with adoptive T cell transfer and with virus-like particles or individual antigens, respectively, have been explored in this model so far. EBV-specific CD8+ T cell priming in humanized mice could provide crucial insights into how cytotoxic lymphocytes against other viruses and tumors might be elicited by vaccination in humans.

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Section: Characteristics Of Cell-mediated Immune Control Against Ebv supporting

confidence: 76%

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Münz

2019

Vaccines

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“…The immunomodulatory agent lenalidomide augments cellular immunity, and in two case reports demonstrated durable efficacy when used for relapsed PTLD (Portell & Nand, ; Laubli et al , ). CAR‐T cells against EBV‐LMP and CD30 are being studied for non‐transplant associated lymphoproliferative disorders (Cho et al , ; Ramos et al , ). If deemed efficacious, there might be a scientific rationale to study their efficacy for treatment of advanced PTLD.…”

Section: Future Directionsmentioning

confidence: 99%

Management of post‐transplant lymphoproliferative disorders

et al. 2018

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The post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of neoplasms that are one of the most serious complications of bone marrow and solid organ transplants. Because these disorders are rare, there are no randomized trials from which to derive optimal treatment. Management can be challenging and must balance the goal of PTLD eradication with the risks of graft rejection, graft-versus-host disease, further delays in immune reconstitution and life-threatening infections, among others. This paper will provide a comprehensive review of PTLD following solid organ transplant and haematopoietic stem cell transplant with a focus on management. Included is a discussion of novel agents that are being studied in clinical trials and, when combined or sequenced with conventional therapy, have the potential to improve outcomes.

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“…MAGE3, NY-ESO) [43]. Engineered T-cells expressing a TCR targeting the latent EBV protein LMP1 presented by HLA-A*02:01 have been generated in a pre-clinical model [44]. Based on our observations, targeting lytic EBV epitopes presented by tumor cells could represent an interesting alternative strategy in EBV-driven cancer, due to the presence of the same EBV epitopes in different patients and the absence of these epitopes in the non-infected normal cells.…”

Section: Discussionmentioning

confidence: 99%

Partial absence of PD-1 expression by tumor-specific CD8⁺T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

Simoni

Becht

et al. 2019

Preprint

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Lymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of CD8 + tumor infiltrating lymphocytes (TILs) in one LELC patient positive for EBV infection in lung tumor cells. Using MHC class I tetramers, we detected two populations of EBV-specific CD8 + TILs, which can be considered as tumor-specific CD8 + T cells, in the tumor of this patient. Transcriptomic analyses of these two populations reveal their distinct exhausted profiles and polyclonal TCR repertoire. High dimensional analyses at single cell level using mass cytometry showed showed that populations of tumor specific CD8 + TILs are phenotypically heterogeneous, although they consistently express CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8 + TILs mostly did not express PD-1, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells for the treatment of LELC patients. These results might also help to explain low rates of checkpoint blockade immunotherapy response for NPC, despite the antigenicity of EBV for both tumor types.

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A novel Epstein–Barr virus-latent membrane protein-1-specific T-cell receptor for TCR gene therapy

Abstract: These data suggest that the novel TCR-targeting LMP1 might allow the potential design of T-cell-based immunotherapeutic strategies against EBV-positive malignancies.

Cited by 38 publications

References 58 publications

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Management of post‐transplant lymphoproliferative disorders

Partial absence of PD-1 expression by tumor-specific CD8⁺T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

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A novel Epstein–Barr virus-latent membrane protein-1-specific T-cell receptor for TCR gene therapy

Abstract: These data suggest that the novel TCR-targeting LMP1 might allow the potential design of T-cell-based immunotherapeutic strategies against EBV-positive malignancies.

Cited by 38 publications

References 58 publications

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Immune Control and Vaccination against the Epstein–Barr Virus in Humanized Mice

Management of post‐transplant lymphoproliferative disorders

Partial absence of PD-1 expression by tumor-specific CD8+T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

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Partial absence of PD-1 expression by tumor-specific CD8⁺T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report