Comparison of Vascular Leak Syndrome in Mice Treated with IL21 or IL2

被引:1
|
作者
Sivakumar, Pallavur V. [1 ]
Garcia, Richard [1 ]
Waggie, Kimberly S. [1 ]
Anderson-Haley, Monica [1 ]
Nelson, Andrew [1 ]
Hughes, Steven D. [1 ]
机构
[1] ZymoGenetics, Seattle, WA USA
关键词
RECOMBINANT HUMAN INTERLEUKIN-21; METASTATIC MELANOMA; CELL ACTIVATION; PHASE-I; IL-21; TOXICITY; EFFICACY; CANCER; LYMPHOCYTES; RESPONSES;
D O I
暂无
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Interleukin 21 (IL21) is a T-cell derived 4-helix-bundle cytokine that has sequence homology to the IL2 family. Recombinant human interleukin 2 (rIL2) is approved for the treatment of metastatic melanoma and renal cell carcinoma. However, toxicity of rIL2, including induction of vascular leak syndrome (VLS), has limited use of this cytokine to a small proportion of eligible patients. Both rIL2 and murine IL21 (mIL21) have potent antitumor efficacy in murine models. The purpose of the current study was to compare the ability of mIL21 and rIL2 to induce vascular leakage in a mouse model. Pulmonary and hepatic uptake of Evans blue dye, serum cytokine levels, spleen cell immunophenotype, and histologic changes in lung and liver were evaluated to detect VLS. High-dose (200 mu g) rIL2 treatment induced vascular leakage in mice, evidenced by inflammatory cell infiltration and fluid extravasation into the lung and liver and increased levels of TNF alpha, IFN gamma, IL5, MCP1, and IL6 in serum. In contrast, an equivalent dose of mIL21 resulted in minimal vascular leakage with no evidence of cytopenia or cytokine production. These results support the use of IL21 as a cancer immunotherapeutic agent, potentially providing an antitumor response without induction of VLS.
引用
收藏
页码:13 / 21
页数:9
相关论文
共 50 条
  • [41] IL21 receptor expression and modulation of gene transcription by interleukin 21.
    Whitters, M
    Calvetti, J
    Johnson, K
    Witek, J
    Byrne, M
    Sibley, LLB
    Collins, M
    Young, D
    JOURNAL OF LEUKOCYTE BIOLOGY, 2001, : 36 - 36
  • [42] A Putative Functional Polymorphism in the IL21 3′-UTR Flanking Region Is Tagged by IL21 Lupus-Associated Variants and Alters Gene Expression in Vitro
    Hughes, Travis
    Sawalha, Amr H.
    ARTHRITIS AND RHEUMATISM, 2011, 63 (10): : S57 - S57
  • [43] Reversal of Vascular Leak with Imatinib: A Role for IL-2?
    Shin, Jae Il
    Eisenhut, Michael
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2014, 190 (01) : 117 - 118
  • [44] CD8+T Cells from Patients with CLL Show Evidence of Granzyme B and Perforin Cytotoxic Capacity, Which Is Enhanced upon Exposure to Exogenous IL2 and/or IL21
    Paraschivescu, Cristina
    Chhabra, Shivani
    Aslam, Rukhsana
    Jung, Byeongho
    Ferrer, Gerardo
    Barrientos, Jacqueline C.
    Rhodes, Joanna M.
    Kolitz, Jonathan E.
    Allen, Steven L.
    Rai, Kanti R.
    Sherry, Barbara
    Chiorazzi, Nicholas
    BLOOD, 2022, 140 : 7000 - 7001
  • [45] Blockade of hyaluronan inhibits IL-2-Induced vascular leak syndrome and maintains effectiveness of IL-2 treatment for metastatic melanoma
    Guan, Hongbing
    Nagarkatti, Prakash S.
    Nagarkatti, Mitzi
    JOURNAL OF IMMUNOLOGY, 2007, 179 (06): : 3715 - 3723
  • [46] IL10/IL2 surrogate cytokine agonists
    Ramadass, Mahalakshmi
    Vivona, Sandro
    Rokkam, Deepti
    Greb, Heiko
    Gangopadhyay, Anu
    Riener, Romina
    Malefyt, Rene de Waal
    Lupardus, Patrick
    Oft, Martin
    Kastelein, Robert
    CANCER RESEARCH, 2022, 82 (12)
  • [47] IL21 and IL21R polymorphisms and their interactive effects on serum IL-21 and IgE levels in patients with chronic hepatitis B virus infection
    Li, Na
    Zhu, Qianqian
    Li, Zhu
    Han, Qunying
    Chen, Jinghong
    Lv, Yi
    Wang, Yawen
    Zeng, Xiaoyan
    Chen, Yanping
    Yang, Cuiling
    Liu, Zhengwen
    HUMAN IMMUNOLOGY, 2013, 74 (05) : 567 - 573
  • [48] IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients
    Chen, Yu-Li
    Chou, Cheng-Yang
    Chang, Ming-Cheng
    Lin, Han-Wei
    Huang, Ching-Ting
    Hsieh, Shu-Feng
    Chen, Chi-An
    Cheng, Wen-Fang
    ENDOCRINE-RELATED CANCER, 2015, 22 (05) : 703 - 711
  • [49] SUPPRESSION OF INTERLEUKIN-2 (IL2) PRODUCTION AND RESPONSE TO IL2 IN EXPERIMENTAL CHAGAS-DISEASE
    HARELBELLAN, A
    JOSKOWICZ, M
    EISEN, H
    FRADELIZI, D
    IMMUNOBIOLOGY, 1984, 167 (1-3) : 211 - 211
  • [50] SIGNAL REQUIREMENT FOR INTERLEUKIN 1(IL 1)-DEPENDENT IL2 PRODUCTION AND IL2 RECEPTOR INDUCTION BY HSB.2 SUBCLONES
    KASAHARA, T
    MUKAIDA, N
    YAGISAWA, H
    KAWAI, T
    SHIOIRINAKANO, K
    JOURNAL OF LEUKOCYTE BIOLOGY, 1987, 42 (05) : 580 - 580