Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)

Savoldo, Barbara; Goss, John A.; Hammer, Markus; Zhang, Lan; Lopez, Teresita; Gee, Adrian P.; Lin, Yu Feng; Quirós-Tejeira, Rubén E.; Reinke, Petra; Schubert, Stephan; Gottschalk, Stephen; Finegold, Milton J.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.

doi:10.1182/blood-2006-05-021782

Cited by 245 publications

(196 citation statements)

References 32 publications

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“…Efficacy of adoptive T-cell therapy using specific EBV cytotoxic T-cells (CTLs) has been demonstrated in patients with EBVrelated post-transplant lymphoproliferative disorder (PTLD) back in 1995 [56,57]. The infusion of EBV specific CTLs was effective in patients as a treatment, in cases of PTLD, and as a prophylaxis, in patients undergoing solid organ transplant and allogeneic stem cell transplantation [58,59]. The initial strategy of administering unselected donor lymphocytes from EBV seropositive stem cells donors was associated with the high risk of developing graft versus host disease (GVHD).…”

Section: Ebv-specific Adoptive Cellular Immunotherapymentioning

confidence: 99%

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

et al. 2016

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Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV‐positive DLBCL can be seen in younger, immunocompetent patients.The diagnosis of EBV‐positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV‐encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined.The International Prognostic Index (IPI), and the Oyama score can be used for risk‐stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor.Patients with EBV‐positive DLBCL should be staged and managed following similar guidelines than patients with EBV‐negative DLBCL. It has been suggested, however, that EBV‐positive patients have a worse prognosis than EBV‐negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV‐positive DLBCL. Am. J. Hematol. 91:530–537, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Ebv-specific Adoptive Cellular Immunotherapymentioning

confidence: 99%

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

et al. 2016

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“…Another obstacle is that SOT patients continue long-term immunosuppressive therapy, and these drugs may suppress the infused cells. Despite these limitations, several groups including our own have reported successful clinical trials using autologous EBVSTs after SOT [50][51][52]. In these studies, adoptive transfer of the patients' own VSTs did not induce organ rejection or produce other adverse events, although in vivo T cell expansion was lower than that observed in HSCT patients who received similar doses of EB-VSTs.…”

Section: Treatment Of Type 3 Latency Tumorsmentioning

confidence: 99%

“…In these studies, adoptive transfer of the patients' own VSTs did not induce organ rejection or produce other adverse events, although in vivo T cell expansion was lower than that observed in HSCT patients who received similar doses of EB-VSTs. Despite the difference in T cell expansion in vivo, which is attributed to more prolonged treatment with immunosuppressive drugs in SOT versus HSCT recipients, response rates in SOT patients were promisingly high [51].…”

Section: Treatment Of Type 3 Latency Tumorsmentioning

confidence: 99%

“…These viruses are classified into highrisk and low-risk groups according to the propensity for malignant progression of the lesions that they cause. Persistent infection of high-risk subtypes, such as HPV- 16,18,31,33,35,39,45,51,52,56,58,59, or 66, has long been known to predispose to the development of cervical cancer [108] and is also associated with carcinomas of the oropharynx and anogenital region. HPV infects basal epithelial cells where viral genomes are persistently maintained as low-copy number episomes [4].…”

Section: Epidemiology and Pathogenesismentioning

confidence: 99%

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Immunotherapy against cancer-related viruses

2016

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Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.

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“…The trial data demonstrate that prophylactic infusions of these viral-specific T cells can prevent clinically-significant EBV infection as well as treat bulky post transplant LPD/lymphoma, EBV-associated NK-cell malignancies (angiocentric lymphomas), and HIV-associated lymphomas. [17][18][19][20][21][22][23][24][25] The implications of clinical trials infusing EBV-specific T cells for adoptive immunotherapy of pediatric neoplasms are potentially far-reaching and five sequelae are described. (i) Bulk (nonclonal) populations of allogeneic T cells, enriched for specificity for EBV, can be safely infused without causing GVHD.…”

Section: Adoptive Cellular Immunotherapy For Ebvmentioning

confidence: 99%

Adoptive cellular immunotherapy for childhood malignancies

Cooper

2007

Bone Marrow Transplant

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Clinical trials have established that T cells have the ability to prevent and treat pathogens and tumors. This is perhaps best exemplified by engraftment of allogeneic T cells in the context of hematopoietic stem-cell transplantation (HSCT), which for over the last 50 years remains one of the best and most robust examples of cell-based therapies for the treatment of hematologic malignancies. Yet, the approach to infuse T cells for treatment of cancer, in general, and pediatric tumors, in particular, generally remains on the sidelines of cancer therapy. This review outlines the current state-of-the-art and provides a rationale for undertaking adoptive immunotherapy trials with emphasis on childhood malignancies.

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Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)

Cited by 245 publications

References 32 publications

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

Immunotherapy against cancer-related viruses

Adoptive cellular immunotherapy for childhood malignancies

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