Sipuleucel-T: Prototype for development of anti-tumor vaccines.
Prostate cancer immunotherapy officially debuted with the recent FDA approval of Sipuleucel-T. The novel trend of cancer immunotherapy relies on the identification of particular tumor-associated antigens, like prostatic acid phosphatase (PAP). Sipuleucel-T consists of autologous dendritic cells activated in vitro with recombinant fusion protein PA2024, PAP-linked to granulocyte-macrophage colony-stimulating factor. Sipuleucel-T represents a prototype for the development of cancer vaccines. Preclinical and clinical data as well as landmark studies for the existing narrow chemotherapy alternatives and early immunotherapy trials will be discussed. The pivotal trial demonstrated a 4.1-month difference of median survival, but with no effect on time to progression in asymptomatic or minimally symptomatic metastatic castrate-resistant patients. Several immunologic effects were observed in the treated population, including antibody and T cell-specific activity to P2024 and PAP. With all new therapies the extent of clinical and objective benefits versus encountered limitations should be evaluated. This review highlights the events and decisions in the process of the development of Sipuleucel-T. We discuss how this successful immunotherapy outcome challenges us to use it as a starting point for variations to or try to amplify practical anticancer progress within the antitumor vaccine paradigm.
Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Estrella
E
Carballido
Mayer
M
Fishman
D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy; D014020:Tissue Extracts / Q000276:immunology* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T
Cancer Immun. 2003 Feb 14;3:2
12747744
J Natl Cancer Inst. 1995 Feb 15;87(4):280-5
7707419
J Clin Oncol. 2007 Feb 20;25(6):669-74
17308271
Blood. 2009 Aug 20;114(8):1537-44
19423728
Expert Opin Biol Ther. 2009 Dec;9(12):1565-75
19916735
Curr Urol Rep. 2010 May;11(3):202-7
20425628
J Clin Oncol. 2000 Dec 1;18(23):3894-903
11099318
N Engl J Med. 2004 Oct 7;351(15):1513-20
15470214
Blood. 2009 Aug 20;114(8):1545-52
19417208
Lancet. 2010 Oct 2;376(9747):1147-54
20888992
Nat Rev Cancer. 2006 Jul;6(7):521-34
16794635
N Engl J Med. 2004 Oct 7;351(15):1502-12
15470213
Cancer Res. 2009 Apr 1;69(7):2801-8
19318557
J Clin Oncol. 2008 Jan 10;26(2):242-5
18182665
Lancet. 2008 Jul 12;372(9633):145-154
18602688
Cancer. 2009 Aug 15;115(16):3670-9
19536890
J Clin Oncol. 2006 Jul 1;24(19):3089-94
16809734
Clin Cancer Res. 2000 Jun;6(6):2175-82
10873066
Clin Cancer Res. 2009 Sep 15;15(18):5937-44
19723649
J Clin Oncol. 2009 Nov 10;27(32):5431-8
19805692
J Clin Oncol. 1999 Nov;17(11):3461-7
10550143
Cancer Res. 2007 Nov 15;67(22):11021-8
18006848
Cancer Immunol Immunother. 1998 Oct;47(2):65-71
9769114
Blood. 2009 Mar 12;113(11):2394-401
19023117
J Immunol. 2001 Jan 1;166(1):678-89
11123353