TABLE 1.
Cancer antigen pilot prioritization: criteria & sub-criteria definitions & weightings
| THERAPEUTIC FUNCTION (Weight of Criteria - 0.32) | ||
|---|---|---|
| Sub-criteria | Definition | Weight of Sub-criteria |
| 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 suggestive |
100.0% (1.0) | |
| Very Strong Data Controlled vaccine trial suggestive |
93.0% (0.93) | |
| Adequate Data Controlled vaccine trial suggestive |
85.0% (0.85) | |
| Fair Data Controlled vaccine trial suggestive |
75.0% (0.75) | |
| Responses in T cell therapy | 65.0% (0.65) | |
| Pre existent immunity/survival correlation |
15.0% (0.15) | |
| Positive appropriate animal models | 10.0% (0.1) | |
| Not applicable (N/A) | 0.0% (0.0) | |
| IMMUNOGENICITY (Weight of Criteria - 0.17) | ||
| Immunogenic in clinical trials | T cell and/or Ab responses elicited in clinical trials |
100.0% (1.0) |
| T cell immunity observed | Spontaneous T cell responses observed in some patients |
39.0% (0.39) |
| Immunogenic in appropriate animal models |
Immunogenic in animal models with natural levels of antigen expression similar to humans |
11.0% (0.11) |
| Ab immunity observed | Spontaneous Ab observed in some patients |
10.0% (0.1) |
| Not applicable (N/A) | 0.0% (0.0) | |
| ONCOGENICITY (Weight of Criteria - 0.15) | ||
| Oncogenic “self” protein | Associated with oncogenic process, i.e., oncogenic “self” protein |
100.0% (1.0) |
| Persistent viral Ag | Persistently expressed viral antigen | 34.0% (0.34) |
| Function uncertain, correlated to decreased survival |
Uncertain function, but increased expression correlated with decreased survival and/or more aggressive or advanced disease |
25.0% (0.25) |
| Tissue differentiation, not oncogenic | Associated with tissue differentiation, but not “oncogenic” |
12.0% (0.12) |
| Tumor-related stroma | Expression on tumor-related stroma, but not on malignant cells |
12.0% (0.12) |
| Not applicable (N/A) | 0.0% (0.0) | |
| SPECIFICITY (Weight of Criteria - 0.15) | ||
| Absolute specificity | Absolutely specific, e.g., mutated oncogene, idiotype protein or viral protein |
100.0% (1.0) |
| Onco-fetal antigen | Antigens expressed in fetus with no or little expression in adult tissue. Includes cancer testis antigens |
54.0% (0.54) |
| Over expressed in cancer | Over expressed in cancer, but expressed in some normal adult tissues |
35.0% (0.35) |
| Abnormal post-translational modification |
Core protein expressed in normal tissue, but expressed in cancer with unique post-translational 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 mutations | Unique random mutations specific to each patient |
10.0% (0.1) |
| Tumor stroma antigen | Normal antigen expressed on tumor stroma |
10.0% (0.1) |
| Not applicable (N/A) | 0.0% (0.0) | |
| EXPRESSION LEVEL & % POSITIVE CELLS (Weight of Criteria - 0.07) | ||
| High level, All cancer cells | Highly expressed on all cancer cells in patients designated for treatment |
100.0% (1.0) |
| High level, Most cancer cells | Highly expressed on most cancer cells in patients designated for treatment |
37.0% (0.37) |
| Lower level, All cancer cells | Lower level of expression on all cancer cells in patients designated for treatment |
23.0% (0.23) |
| Lower level, Most cancer cells | Lower level of expression on most cancer cells in patients designated for treatment |
8.0% (0.08) |
| Not applicable (N/A) | 0.0% (0.0) | |
| STEM CELL EXPRESSION (Weight of Criteria - 0.05) | ||
| Stem cell expression, presumptive | Evidence for expression on putative cancer stem cells |
100.0% (1.0) |
| No info concerning stem cells - but on all stages from premalignant to metastatic |
Present at all stages of tumor development, from premalignant to metastatic cancer cells, but without information about putative stem cells |
66.0% (0.66) |
| No info concerning stem cells, but on most cancer cells |
Expression on the all or most cancer cells, but without information about putative stem cells |
20.0% (0.2) |
| Not applicable (N/A) | 0.0% (0.0) | |
| NUMBER OF PATIENTS WITH ANTIGEN POSITIVE CANCERS (Weight of Criteria - 0.04) | ||
| Many patients, high level | High level of expression in many patients with a particular tumor type |
100.0% (1.0) |
| Many patients, lower level | Low level of expression in many patients with a particular tumor type |
16.0% (0.16) |
| All patients/ unique antigens | Unique antigens from random mutations presumed to be present in all patients |
14.0% (0.14) |
| Few patients, high level | High level of expression in a small subset of patients with a particular tumor type |
11.0% (0.11) |
| Not applicable (N/A) | 0.0% (0.0) | |
| NUMBER OF EPITOPES (Weight of Criteria - 0.04) | ||
| Longer antigen | Longer antigen with multiple epitopes and the potential to bind to most MHC molecules |
100.0% (1.0) |
| Short antigenic segment | Short antigenic segment with one or few epitopes and the potential to bind to only selected MHC molecules |
13.0% (0.13) |
| CELLULAR LOCATION OF EXPRESSION (Weight of Criteria - 0.02) | ||
| Cell surface expression; no or little circulating Ag |
Normally expressed on the cell surface with no or little circulating antigen |
100.0% (1.0) |
| Internal with MHC presentation | Internal only with MHC presentation | 95.0% (0.95) |
| Cell surface expression; and circulating Ag |
Normally expressed on the cell surface with substantial circulating antigen |
25.0% (0.25) |
| Not applicable (N/A) | 0.0% (0.0) | |