Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs

Seok Goo Cho; Nayoun Kim; Hyun Jung Sohn; Suk Kyeong Lee; Sang Taek Oh; Hyun Joo Lee; Hyun Il Cho; Hyeon Woo Yim; Seung Eun Jung; Gyeongsin Park; Joo Hyun Oh; Byung Ock Choi; Sung Won Kim; Soo Whan Kim; Nak Gyun Chung; Jong Wook Lee; Young Seon Hong; Tai Gyu Kim

doi:10.1038/mt.2015.91

Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs

Seok Goo Cho, Nayoun Kim, Hyun Jung Sohn, Suk Kyeong Lee, Sang Taek Oh, Hyun Joo Lee, Hyun Il Cho, Hyeon Woo Yim, Seung Eun Jung, Gyeongsin Park, Joo Hyun Oh, Byung Ock Choi, Sung Won Kim, Soo Whan Kim, Nak Gyun Chung, Jong Wook Lee, Young Seon Hong, Tai Gyu Kim

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Abstract

Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10 7 LMP1/2a CTLs/m 2. Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.

Original language	English
Pages (from-to)	1401-1409
Number of pages	9
Journal	Molecular Therapy
Volume	23
Issue number	8
DOIs	https://doi.org/10.1038/mt.2015.91
State	Published - 1 Aug 2015

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© The American Society of Gene & Cell Therapy.

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10.1038/mt.2015.91

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Cho, S. G., Kim, N., Sohn, H. J., Lee, S. K., Oh, S. T., Lee, H. J., Cho, H. I., Yim, H. W., Jung, S. E., Park, G., Oh, J. H., Choi, B. O., Kim, S. W., Kim, S. W., Chung, N. G., Lee, J. W., Hong, Y. S., & Kim, T. G. (2015). Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs. Molecular Therapy, 23(8), 1401-1409. https://doi.org/10.1038/mt.2015.91

@article{e07aa108c78e418495a26d9d284dabb1,

title = "Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs",

abstract = "Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10 7 LMP1/2a CTLs/m 2. Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.",

author = "Cho, {Seok Goo} and Nayoun Kim and Sohn, {Hyun Jung} and Lee, {Suk Kyeong} and Oh, {Sang Taek} and Lee, {Hyun Joo} and Cho, {Hyun Il} and Yim, {Hyeon Woo} and Jung, {Seung Eun} and Gyeongsin Park and Oh, {Joo Hyun} and Choi, {Byung Ock} and Kim, {Sung Won} and Kim, {Soo Whan} and Chung, {Nak Gyun} and Lee, {Jong Wook} and Hong, {Young Seon} and Kim, {Tai Gyu}",

note = "Publisher Copyright: {\textcopyright} The American Society of Gene & Cell Therapy.",

year = "2015",

month = aug,

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doi = "10.1038/mt.2015.91",

language = "English",

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Cho, SG, Kim, N, Sohn, HJ, Lee, SK, Oh, ST, Lee, HJ, Cho, HI, Yim, HW , Jung, SE, Park, G, Oh, JH , Choi, BO , Kim, SW , Kim, SW , Chung, NG, Lee, JW, Hong, YS & Kim, TG 2015, 'Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs', Molecular Therapy, vol. 23, no. 8, pp. 1401-1409. https://doi.org/10.1038/mt.2015.91

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AU - Cho, Seok Goo

AU - Kim, Nayoun

AU - Sohn, Hyun Jung

AU - Lee, Suk Kyeong

AU - Oh, Sang Taek

AU - Lee, Hyun Joo

AU - Cho, Hyun Il

AU - Yim, Hyeon Woo

AU - Jung, Seung Eun

AU - Park, Gyeongsin

AU - Oh, Joo Hyun

AU - Choi, Byung Ock

AU - Kim, Sung Won

AU - Kim, Soo Whan

AU - Chung, Nak Gyun

AU - Lee, Jong Wook

AU - Hong, Young Seon

AU - Kim, Tai Gyu

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10 7 LMP1/2a CTLs/m 2. Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.

AB - Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10 7 LMP1/2a CTLs/m 2. Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL.

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Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated with Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs

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