mercredi 10 août 2011

Focus: the prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research




The purpose of the National Cancer Institute pilot project to prioritize cancer antigens was to develop a well-vetted, priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was for the National Cancer Institute to test a new approach for prioritizing translational research opportunities based on an analytic hierarchy process for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the predefined criteria for the selected antigens, and ranking the antigens based on the predefined, preweighted criteria. Using the pairwise approach, the result of criteria weighting, in descending order, was as follows: (a) therapeutic function, (b) immunogenicity, (c) role of the antigen in oncogenicity, (d) specificity, (e) expression level and percent of antigen-positive cells, (f) stem cell expression, (g) number of patients with antigen-positive cancers, (h) number of antigenic epitopes, and (i) cellular location of antigen expression. None of the 75 antigens had all of the characteristics of the ideal cancer antigen. However, 46 were immunogenic in clinical trials and 20 of them had suggestive clinical efficacy in the "therapeutic function" category. These findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.

Source: The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Cheever MA (mcheever@seattlecca.org), Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, Mellman I, Prindiville SA, Viner JL, Weiner LM, Matrisian LM. Clin Cancer Res. 2009 Sep 1;15(17):5323-37.


From the paper:
Priority-ranked list of cancer vaccine target antigens based on predefined and preweighted
objective criteria developed by a panel of content experts.







1
WT1
26
PAP
51
GloboH
2
MUC1
27
ML-IAP
52
ETV6-AML
3
LMP2
28
AFP
53
NY-BR-1
4
HPV E6 E7
29
EpCAM
54
RGS5
5
EGFRvIII
30
ERG (TMPRSS2 ETS fusion gene)
55
SART3
6
HER-2/neu
31
NA17
56
STn
7
Idiotype
32
PAX3
57
Carbonic anhydrase IX
8
MAGE A3
33
ALK
58
PAX5
9
p53 nonmutant
34
Androgen receptor
59
OY-TES1
10
NY-ESO-1
35
Cyclin B1
60
Sperm protein 17
11
PSMA
36
Polysialic acid
61
LCK
12
GD2
37
MYCN
62
HMWMAA
13
CEA
38
RhoC
63
AKAP-4
14
MelanA/MART1
39
TRP-2
64
SSX2
15
Ras mutant
40
GD3
65
XAGE 1
16
gp100
41
Fucosyl GM1
66
B7H3
17
p53 mutant
42
Mesothelin
67
Legumain
18
Proteinase3 (PR1)
43
PSCA
68
Tie 2
19
bcr-abl
44
MAGE A1
69
Page4
20
Tyrosinase
45
sLe(animal)
70
VEGFR2
21
Survivin
46
CYP1B1
71
MAD-CT-1
22
PSA
47
PLAC1
72
FAP
23
hTERT
48
GM3
73
PDGFR-β
24
Sarcoma translocation breakpoints
49
BORIS
74
MAD-CT-2
25
EphA2
50
Tn
75
Fos-related antigen 1








Aucun commentaire:

Enregistrer un commentaire