IRX-2 increases the T cell-specific immune response to protein/peptide vaccines.

作者: Paul H. Naylor , Karla E. Hernandez , April E. Nixon , Harvey J. Brandwein , Gabriel P. Haas

DOI: 10.1016/J.VACCINE.2010.08.014

关键词:

摘要: Therapeutic cancer vaccines are attractive due to the prospect of specificity and their lack toxicity; however, clinical development has been hampered by several biologic challenges. One most important challenges is relative effective cellular immune adjuvants. Effective physiologic responses characterized local generation a complex cytokine environment that activates regulates multiple cell types. IRX-2 primary cell-derived with physiological levels active components, produced under pharmaceutical standards. The hypothesis amplifies T response defined antigens was assessed in mice measuring cell-specific peptide dominant mouse (NFT) derived from human prostate-specific membrane antigen (PSMA). enhances NFT when were delivered either via irradiated cells expressing PSMA, Incomplete Freund's adjuvant (IFA) or conjugated KLH. activity measured spleen lymph nodes IFN-γ ELISpot and/or secretion over 6 days vivo peptide-specific delayed-type hypersensitivity reaction (DTH). Further more, single administration not as compared 4 9 additional administrations which sufficient enhance antigens. influence on B ovalbumin it used carrier protein ELISA. commercially available combination (MPL+TDM squalene/Tween 80) based literature potent murine systems. In assay superior while also increased antibody titer, adjuvant. Mice immunized exhibited delayed tumor progression following challenge PSMA-expressing cells. These studies demonstrate an immunomodulator preferentially associated Based these studies, candidate for evaluation variety preclinical vaccine delivery systems well trials candidates.

参考文章(34)
James E. Egan, Karen J. Quadrini, Frances Santiago-Schwarz, John W. Hadden, Harvey J. Brandwein, Kathy L. Signorelli, IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro. Journal of Immunotherapy. ,vol. 30, pp. 624- 633 ,(2007) , 10.1097/CJI.0B013E3180691593
Katsuyuki Kuratsukuri, Tomomichi Sone, Ching Y. Wang, Nobuyasu Nishisaka, Richard F. Jones, Gabriel P. Haas, Inhibition of prostate-specific membrane antigen (PSMA)-positive tumor growth by vaccination with either full-length or the C-terminal end of PSMA. International Journal of Cancer. ,vol. 102, pp. 244- 249 ,(2002) , 10.1002/IJC.10700
Benjamin A Tjoa, Gerald P Murphy, Development of dendritic-cell based prostate cancer vaccine Immunology Letters. ,vol. 74, pp. 87- 93 ,(2000) , 10.1016/S0165-2478(00)00254-6
Lothar H. Finke, Kerry Wentworth, Brent Blumenstein, Natalie S. Rudolph, Hyam Levitsky, Axel Hoos, Lessons from randomized phase III studies with active cancer immunotherapies--outcomes from the 2006 meeting of the Cancer Vaccine Consortium (CVC). Vaccine. ,vol. 25, ,(2007) , 10.1016/J.VACCINE.2007.06.067
Anna-K. Thomas-Kaskel, Robert Zeiser, Rosa Jochim, Christian Robbel, Wolfgang Schultze-Seemann, Cornelius F. Waller, Hendrik Veelken, Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival. International Journal of Cancer. ,vol. 119, pp. 2428- 2434 ,(2006) , 10.1002/IJC.22097
R HENDERSON, S MOSSMAN, N NAIRN, M CHEEVER, Cancer vaccines and immunotherapies: emerging perspectives. Vaccine. ,vol. 23, pp. 2359- 2362 ,(2005) , 10.1016/J.VACCINE.2005.01.082
Katsuyuki Kuratsukuri, Nobuyasu Nishisaka, Richard F Jones, Ching Y Wang, Gabriel P Haas, Clinical trials of immunotherapy for advanced prostate cancer. Urologic Oncology-seminars and Original Investigations. ,vol. 5, pp. 265- 273 ,(2000) , 10.1016/S1078-1439(00)00086-7
B.A. Tjoa, S.J. Simmons, V.A. Bowes, H. Ragde, M. Rogers, A. Elgamal, G.M. Kenny, O.E. Cobb, R.C. Ireton, M.J. Troychak, M.L. Salgaller, A.L. Boynton, G.P. Murphy, Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides. The Prostate. ,vol. 36, pp. 39- 44 ,(1998) , 10.1002/(SICI)1097-0045(19980615)36:1<39::AID-PROS6>3.0.CO;2-6
J Hadden, E Verastegui, J.L Barrera, M Kurman, A Meneses, J.W Zinser, J de la Garza, E Hadden, A trial of IRX-2 in patients with squamous cell carcinomas of the head and neck International Immunopharmacology. ,vol. 3, pp. 1073- 1081 ,(2003) , 10.1016/S1567-5769(03)00029-8