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.

Free article available at: http://clincancerres.aacrjournals.org/content/15/17/5323.full.pdf+html

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