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Updated: Jul 5, 2026
An Efficient and Simple Method to Establish NK and T Cell Lines from Patients with Chronic Active Epstein-Barr Virus Infection
Published on: March 30, 2018
An Epstein-Barr virus positive natural killer lymphoma xenograft derived for drug testing
Susan Li Er Loong1, Jacqueline Siok Gek Hwang, Soon-Thye Lim
1Division of Cellular and Molecular Research, Department of Radiation Oncology, National Cancer Centre, Singapore.
Abstract:
Natural killer (NK) lymphomas occurring more frequently in the Far East and South America respond poorly to anthracycline-based regimens. Here we report an in vivo NK lymphoma xenograft (NK-S1) derived from the testicular metastasis of a patient with an extranodal NK lymphoma (nasal type). The NK-S1 xenograft, established in severe combined immune deficient (SCID) mice retained the same imunophenotypic features as the original tumor. NK-S1 disseminated intra-abdominally to the testis, intestine and liver. Although doxorubicin, rapamycin, bevacizumab, rapamycin-doxorubicin, and bevacizumab-doxorubicin had no effects on the growth of subcutaneous NK-S1 xenografts, intraperitoneal (IP) delivery of cyclophosphamide caused complete tumor regression; this tumor regression was associated with apoptosis, upregulation of activated caspase-3, and cleaved Poly(ADP-ribose) polymerase (PARP). In an IP model of NK lymphoma, cyclophosphamide also prolonged the survival of mice and potently inhibited tumor dissemination and ascites formation. Our data suggest that the NK-S1 xenograft is a useful tool for screening preclinical drugs, and cyclophosphamide may be a useful drug for the treatment of this disease.
Insights
A new natural killer (NK) lymphoma xenograft model (NK-S1) was developed. Cyclophosphamide effectively treated this model, showing complete tumor regression and improved survival in mice.
Area of Science:
- Oncology
- Immunology
- Translational Research
Background:
- Extranodal natural killer (NK) lymphomas are prevalent in East Asia and South America.
- These lymphomas often exhibit resistance to conventional anthracycline-based chemotherapy.
Purpose of the Study:
- To establish and characterize a novel in vivo xenograft model of NK lymphoma.
- To evaluate the efficacy of various therapeutic agents, including cyclophosphamide, in preclinical models of NK lymphoma.
Main Methods:
- An NK lymphoma xenograft (NK-S1) was derived from patient metastasis and established in severe combined immune deficient (SCID) mice.
- The NK-S1 model was used to assess the effects of doxorubicin, rapamycin, bevacizumab, and cyclophosphamide on tumor growth and dissemination.
- Tumor regression was analyzed by examining apoptosis, activated caspase-3, and cleaved Poly(ADP-ribose) polymerase (PARP) expression.
Main Results:
- The NK-S1 xenograft retained the immunophenotypic features of the original tumor and disseminated within the mice.
- Subcutaneous NK-S1 xenografts showed no response to doxorubicin, rapamycin, or bevacizumab.
- Intraperitoneal cyclophosphamide induced complete tumor regression, apoptosis, and upregulation of cleaved caspase-3 and PARP.
- In an intraperitoneal NK lymphoma model, cyclophosphamide prolonged survival and inhibited tumor spread and ascites formation.
Conclusions:
- The NK-S1 xenograft is a valuable preclinical tool for drug screening in NK lymphoma.
- Cyclophosphamide demonstrates significant therapeutic potential for treating extranodal NK lymphoma, particularly in disseminated disease.
