Table 1.

Cancer antigen pilot prioritization: criteria and subcriteria, definitions, and weightings

SubcriteriaDefinitionWeight of subcriteria
Therapeutic function (weight of criteria, 0.32)
    Controlled vaccine trial suggestive (data ranked as being superb, very strong, adequate, or fair)Clinical trial data showing that a vaccine induced clinical responses in at least a small number of patients or provided suggestive evidence of benefit vs controls
    Superb data controlled vaccine trial suggestive100.0% (1.0)
    Very strong data controlled vaccine trial suggestive93.0% (0.93)
    Adequate data controlled vaccine trial suggestive85.0% (0.85)
    Fair data controlled vaccine trial suggestive75.0% (0.75)
    Responses in T-cell therapy65.0% (0.65)
    Preexistent immunity/survival correlation15.0% (0.15)
    Positive appropriate animal models10.0% (0.1)
    Not applicable0.0% (0.0)
Immunogenicity (weight of criteria, 0.17)
    Immunogenic in clinical trialsT-cell and/or antibody responses elicited in clinical trials100.0% (1.0)
    T-cell immunity observedSpontaneous T-cell responses observed in some patients39.0% (0.39)
    Immunogenic in appropriate animal modelsImmunogenic in animal models with natural levels of antigen expression similar to humans11.0% (0.11)
    Antibody immunity observedSpontaneous antibody observed in some patients10.0% (0.1)
    Not applicable0.0% (0.0)
Oncogenicity (weight of criteria, 0.15)
    Oncogenic “self” proteinAssociated with oncogenic process (i.e., oncogenic “self” protein)100.0% (1.0)
    Persistent viral antigenPersistently expressed viral antigen34.0% (0.34)
    Function uncertain, correlated to decreased survivalUncertain function, but increased expression correlated with decreased survival and/or more aggressive or advanced disease25.0% (0.25)
    Tissue differentiation, not oncogenicAssociated with tissue differentiation, but not oncogenic12.0% (0.12)
    Tumor-related stromaExpression on tumor-related stroma, but not on malignant cells12.0% (0.12)
    Not applicable0.0% (0.0)
Specificity (weight of criteria, 0.15)
    Absolute specificityAbsolutely specific (e.g., mutated oncogene, idiotype protein, or viral protein)100.0% (1.0)
    Oncofetal antigenAntigens expressed in fetus with no or little expression in adult tissue (includes cancer testis antigens)54.0% (0.54)
    Overexpressed in cancerOverexpressed in cancer, but expressed in some normal adult tissues35.0% (0.35)
    Abnormal posttranslational modificationCore protein expressed in normal tissue, but expressed in cancer with unique posttranslational changes (e.g., glycosylation or phosphorylation)23.0% (0.23)
    Tissue specific (expendable tissue)Tissue-specific expression in normal adult tissue relatively expendable for survival (e.g., prostate and melanocytes)21.0% (0.21)
    Unique random mutationsUnique random mutations specific to each patient10.0% (0.1)
    Tumor stroma antigenNormal antigen expressed on tumor stroma10.0% (0.1)
    Not applicable0.0% (0.0)
Expression level and % positive cells (weight of criteria, 0.07)
    High level, all cancer cellsHighly expressed on all cancer cells in patients designated for treatment100.0% (1.0)
    High level, most cancer cellsHighly expressed on most cancer cells in patients designated for treatment37.0% (0.37)
    Lower level, all cancer cellsLower level of expression on all cancer cells in patients designated for treatment23.0% (0.23)
    Lower level, most cancer cellsLower level of expression on most cancer cells in patients designated for treatment8.0% (0.08)
    Not applicable0.0% (0.0)
Stem cell expression (weight of criteria, 0.05)
    Stem cell expression, presumptiveEvidence for expression on putative cancer stem cells100.0% (1.0)
    No info about stem cells, but on all stages from premalignant to metastaticPresent at all stages of tumor development, from premalignant to metastatic cancer cells, but without information about putative stem cells66.0% (0.66)
    No info about stem cells, but on most cancer cellsExpression on all or most cancer cells, but without information about putative stem cells20.0% (0.2)
    Not applicable0.0% (0.0)
No. patients with antigen-positive cancers (weight of criteria, 0.04)
    Many patients, high levelHigh level of expression in many patients with a particular tumor type100.0% (1.0)
    Many patients, lower levelLow level of expression in many patients with a particular tumor type16.0% (0.16)
    All patients/unique antigensUnique antigens from random mutations presumed to be present in all patients14.0% (0.14)
    Few patients, high levelHigh level of expression in a small subset of patients with a particular tumor type11.0% (0.11)
    Not applicable0.0% (0.0)
No. epitopes (weight of criteria, 0.04)
    Longer antigenLonger antigen with multiple epitopes and the potential to bind to most MHC molecules100.0% (1.0)
    Short antigenic segmentShort antigenic segment with one or few epitopes and the potential to bind to only selected MHC molecules13.0% (0.13)
Cellular location of expression (weight of criteria, 0.02)
    Cell surface expression, no or little circulating antigenNormally expressed on the cell surface with no or little circulating antigen100.0% (1.0)
    Internal with MHC presentationInternal only with MHC presentation95.0% (0.95)
    Cell surface expression, and circulating antigenNormally expressed on the cell surface with substantial circulating antigen25.0% (0.25)
    Not applicable0.0% (0.0)