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

Abstract

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.

Figure 1

Criteria for an idea cancer antigen were weighted by pair-wise comparison and the resulting relative weights are indicated. Therapeutic function was considered the most important criteria, and was more than twice (0.32/0.15) as important as specificity or oncogenicity.

Figure 2

Cancer antigen pilot prioritization: representation of ranking based on predefined and preweighted criteria and sub-criteria. Inset indicates the color used to designate each criterion and its relative weight. The number at the end of each bar indicates the relative rank of that antigen.

Figure 3

Representation of ranking following exclusion of “therapeutic efficacy” and “immunogenicity”. Inset indicates the color used to designate each criterion and its relative weight. The number at the end of each bar indicates the relative rank of that antigen.