دورية أكاديمية
Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2.
| العنوان: | Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2. |
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| المؤلفون: | Roychowdhury S; Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA., May KF Jr, Tzou KS, Lin T, Bhatt D, Freud AG, Guimond M, Ferketich AK, Liu Y, Caligiuri MA |
| المصدر: | Cancer research [Cancer Res] 2004 Nov 01; Vol. 64 (21), pp. 8062-7. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Print ISSN: 0008-5472 (Print) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Immunotherapy, Adoptive*, Interleukin-15/*therapeutic use , Interleukin-2/*therapeutic use , Neoplasms, Experimental/*therapy , T-Lymphocytes/*immunology, Animals ; Female ; Immunologic Memory ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental/immunology ; Proto-Oncogene Proteins c-bcl-2/analysis |
| مستخلص: | Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3 versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy. |
| معلومات مُعتمدة: | CA068458 United States CA NCI NIH HHS; CA58033 United States CA NCI NIH HHS; CA95426 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Interleukin-15) 0 (Interleukin-2) 0 (Proto-Oncogene Proteins c-bcl-2) |
| تواريخ الأحداث: | Date Created: 20041103 Date Completed: 20041130 Latest Revision: 20071114 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1158/0008-5472.CAN-04-1860 |
| PMID: | 15520217 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0008-5472 |
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| DOI: | 10.1158/0008-5472.CAN-04-1860 |