Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study

Kim, Won Seog; Oki, Yasuhiro; Kim, Seok Jin; Yoon, Sang Eun; Ardeshna, Kirit M.; Lin, Yi; Ruan, Jia; Porcu, Pierluigi; Brammer, Jonathan E.; Jacobsen, Eric; Yoon, Dok Hyun; Suh, Cheolwon; Suarez, Félipe; Radford, John; Budde, Lihua E.; Kim, Jin Seok; Bachy, Emmanuel; Lee, Hun Ju; Bollard, Catherine M.; Jaccard, Arnaud; Kang, Hye Jin; Inman, Shannon; Murray, Maryann; Combs, Katherin E; Lee, Daniel Y; Advani, Ranjana H.; Gunter, Kurt C.; Rooney, Cliona M.; Heslop, Helen E.

doi:10.1007/s00277-021-04558-0

Cited by 19 publications

(17 citation statements)

References 30 publications

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“…The ORR was 50%, with a CR rate of 30%. The median PFS was 12.3 months [103]. No grade 3 or 4 adverse events were observed.…”

Section: Other Immunotherapies Including Cellular Therapymentioning

confidence: 88%

“…Production of active autologous EBV-specific CTL targeting these latency type II EBV-positive tumours would require the use of adenoviral vector transduced dendritic cells expressing LMP1 and 2, and EBV-transformed lymphoblastoid cell lines as antigen-presenting cells to activate and expand EBV-antigen specific CTL [102]. In a recent phase II study of 47 patients with R/R NK/T-cell lymphoma, autologous EBVspecific CTL was successfully generated in 32 cases, with 15 patients subsequently infused with the products [103]. Ten of them had active lymphoma at the time of treatment and received a median of four doses of EBV-specific CTL.…”

Section: Other Immunotherapies Including Cellular Therapymentioning

confidence: 99%

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Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

Tse

Kwong

2022

Cancers

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Natural killer (NK)/T-cell lymphomas are aggressive malignancies. Epstein–Barr virus (EBV) infection in lymphoma cells is invariable. NK/T-cell lymphomas are divided into nasal, non-nasal, and disseminated subtypes. Nasal NK/T-cell lymphomas involve the nasal cavity and the upper aerodigestive tract. Non-nasal NK/T-cell lymphomas involve the skin, gastrointestinal tract, testis and other extranodal sites. Disseminated NK/T-cell lymphoma involves multiple organs, rarely presenting with a leukaemic phase. Lymphoma cells are positive for CD3ε (not surface CD3), CD56, cytotoxic molecules and EBV-encoded small RNA. There is a predilection for Asian and Central/South American populations. Genome-wide association studies have identified lymphoma susceptibility loci in Asian patients. Positron emission tomography computed tomography and plasma EBV DNA quantification are crucial evaluations at diagnosis and follow-up. Stage I/II patients typically receive non-athracycline regimens containing asparaginse, together with sequential/concurrent radiotherapy. Anthracycline-containing regimens are ineffective. Stage III/IV patients are treated with asparaginase-containing regimens, followed by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable cases. Autologous HSCT does not improve outcome. In relapsed/refractory patients, novel approaches are needed, involving PD1/PD-L1 targeting, EBV-specific cytotoxic T-cells, and monoclonal antibodies. Small molecules including histone deacetylase inhibitors may be beneficial in selected patients. Future strategies may include targeting of signalling pathways and driver mutations.

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“…The ORR was 50%, with a CR rate of 30%. The median PFS was 12.3 months [103]. No grade 3 or 4 adverse events were observed.…”

Section: Other Immunotherapies Including Cellular Therapymentioning

confidence: 88%

Section: Other Immunotherapies Including Cellular Therapymentioning

confidence: 99%

Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

Tse

Kwong

2022

Cancers

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“…Interestingly, T-cell products appeared heterogeneous, and responders generally received higher numbers of LMP2-reactive T-cells than non-responders, suggesting that outcomes may be improved further by enriching the T-cell product for LMP2-specific T-cells [ 110 ]. These results were extended further in a phase 2 clinical trial to develop autologous EBV-specific T-cells (baltaleucel T) for treatment and prevention of relapse in advanced, relapsed ENKTL [ 58 ]. Autologous polyspecific EBV-targeting T-cells were created by simulation of the patients’ T-cells derived from the peripheral blood with antigen-presenting cells pulsed with Pepmixes derived from EBV targets LMP1, LMP2, BamH1 rightward-open reading frame 1 (BARF1), and EBNA1 [ 58 ].…”

Section: Targeting Ebv In the Treatment Of Enktlmentioning

confidence: 99%

“…These results were extended further in a phase 2 clinical trial to develop autologous EBV-specific T-cells (baltaleucel T) for treatment and prevention of relapse in advanced, relapsed ENKTL [ 58 ]. Autologous polyspecific EBV-targeting T-cells were created by simulation of the patients’ T-cells derived from the peripheral blood with antigen-presenting cells pulsed with Pepmixes derived from EBV targets LMP1, LMP2, BamH1 rightward-open reading frame 1 (BARF1), and EBNA1 [ 58 ]. Among 47 patients that enrolled, 15 patients received a median of four EBV-specific T-cell doses, while the rest did not receive the T-cell product due to manufacturing failure, rapid disease progression before the cells could be given, or death [ 58 ].…”

Section: Targeting Ebv In the Treatment Of Enktlmentioning

confidence: 99%

“…Autologous polyspecific EBV-targeting T-cells were created by simulation of the patients’ T-cells derived from the peripheral blood with antigen-presenting cells pulsed with Pepmixes derived from EBV targets LMP1, LMP2, BamH1 rightward-open reading frame 1 (BARF1), and EBNA1 [ 58 ]. Among 47 patients that enrolled, 15 patients received a median of four EBV-specific T-cell doses, while the rest did not receive the T-cell product due to manufacturing failure, rapid disease progression before the cells could be given, or death [ 58 ]. Among the T-cell recipients, 10 patients had active ENKTL at the time of product infusion and demonstrated a 30% complete response (CR) and a 50% overall response rate (ORR) [ 58 ].…”

Section: Targeting Ebv In the Treatment Of Enktlmentioning

confidence: 99%

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Extranodal Natural Killer/T-Cell Lymphomas: Current Approaches and Future Directions

Reneau

Shindiapina

Braunstein

et al. 2022

JCM

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Extranodal natural killer/T(NK/T)-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma that typically presents with an isolated nasal mass, but a sizeable minority present with advanced stage disease and have a significantly poorer prognosis. Those with limited disease are standardly treated with chemotherapy and radiation while those with advanced stage disease are treated with L-asparaginase containing chemotherapy regimens. The addition of modern radiation therapy techniques and the incorporation of L-asparaginase into chemotherapy regimens have significantly improved outcomes in this disease, but relapses and death from relapsed disease remain frequent. Given the high rate of relapse, several novel therapies have been evaluated for the treatment of this disease. In this review, we explore the current standard of care for ENKTL as well as novel therapies that have been evaluated for its treatment and the biologic understanding behind these therapies.

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Immunologic Therapies in Development forEBVDriven Lymphoid Malignancies

Yongsheng CHAN,

Jin Kim,

Thye LIM

et al. 2024

Precision Cancer Therapies Vol 2 ‐ Immunologic Approaches for the Treatment of Lymphoid Malignancies ‐ From Concept to Practice

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Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study

Cited by 19 publications

References 30 publications

Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

Extranodal Natural Killer/T-Cell Lymphomas: Current Approaches and Future Directions

Immunologic Therapies in Development forEBVDriven Lymphoid Malignancies

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