Folate-conjugated immunoglobulin targets melanoma tumor cells for NK cell effector functions.

作者: Cassandra C. Skinner , Elizabeth L. McMichael , Alena C. Jaime-Ramirez , Zachary B. Abrams , Robert J. Lee

DOI: 10.1097/CMR.0000000000000258

关键词:

摘要: The folate receptor (FR) is overexpressed on the vascular side of cancerous cells including those breast, ovaries, testes, and cervix. We hypothesized that a folate-conjugated immunoglobulin (F-IgG) would bind to FR melanoma tumor target these for lysis by natural killer (NK) cells. Folate expression was confirmed in Mel-39 (human melanoma) cell line flow cytometry immunoblot analysis using KB oral epithelial) F01 as positive negative control, respectively. FR-positive FR-negative lines were treated with F-IgG or control G presence absence cytokines determine NK ability lyse lines. activation significantly upregulated Mel 39 increased following treatment compared at all effector : target (E : T) ratios (P<0.01). This trend further stimulation activating cytokine interleukin-12. production such interferon-gamma, macrophage inflammatory protein 1α, regulated normal T-cell expressed secreted (RANTES) also response costimulation interleukin-12 F-IgG-coated controls In contrast, did not had no significant effect production. research indicates potential use its induce an immune from against cells, which can be addition cytokines.

参考文章(53)
Robin Parihar, William E. Carson, Novel cytokines in the treatment of malignancies. Cancer treatment and research. ,vol. 126, pp. 353- 373 ,(2005) , 10.1007/0-387-24361-5_15
C.P. Leamon, P.S. Low, Cytotoxicity of momordin-folate conjugates in cultured human cells. Journal of Biological Chemistry. ,vol. 267, pp. 24966- 24971 ,(1992) , 10.1016/S0021-9258(19)73992-1
Alena Cristina Jaime-Ramirez, Bethany L. Mundy-Bosse, SriVidya Kondadasula, Natalie B. Jones, Julie M. Roda, Aruna Mani, Robin Parihar, Volodymyr Karpa, Tracey L. Papenfuss, Krista M. LaPerle, Elizabeth Biller, Amy Lehman, Abhik Ray Chaudhury, David Jarjoura, Richard W. Burry, William E. Carson, IL-12 Enhances the Antitumor Actions of Trastuzumab via NK Cell IFN-γ Production Journal of Immunology. ,vol. 186, pp. 3401- 3409 ,(2011) , 10.4049/JIMMUNOL.1000328
Philip S Low, Asok C Antony, Folate receptor-targeted drugs for cancer and inflammatory diseases Advanced Drug Delivery Reviews. ,vol. 56, pp. 1055- 1058 ,(2004) , 10.1016/J.ADDR.2004.02.003
Megan A Cooper, Todd A Fehniger, Michael A Caligiuri, The biology of human natural killer-cell subsets. Trends in Immunology. ,vol. 22, pp. 633- 640 ,(2001) , 10.1016/S1471-4906(01)02060-9
Toshiyuki Takai, Min Li, Diana Sylvestre, Raphael Clynes, Jeffrey V. Ravetch, FcR γ chain deletion results in pleiotrophic effector cell defects Cell. ,vol. 76, pp. 519- 529 ,(1994) , 10.1016/0092-8674(94)90115-5
T Barrette, A Pandey, AM Chinnaiyan, ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform Neoplasia. ,vol. 6, pp. 1- 6 ,(2004) , 10.1016/S1476-5586(04)80047-2
Hong Li, Yanhui Lu, Longzhu Piao, Jun Wu, Xiaojuan Yang, Sri Vidya Kondadasula, William E. Carson, Robert J. Lee, Folate-immunoglobulin G as an anticancer therapeutic antibody. Bioconjugate Chemistry. ,vol. 21, pp. 961- 968 ,(2010) , 10.1021/BC900545H
Vadim?Y. Taraban, Tania?F. Rowley, Lyn O'Brien, H.?T.?Claude Chan, Linsey?E. Haswell, Michael?H.?A. Green, Alison?L. Tutt, Martin?J. Glennie, Aymen Al-Shamkhani, Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses. European Journal of Immunology. ,vol. 32, pp. 3617- 3627 ,(2002) , 10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M