Table 5C.
| Patients | IL-4 | Summary of post-vaccination anti-HER2 response | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| ECD | ICD | ECD | ICD | ECD/ICD | |||||||
| Pre | Post | Pre | Post | Vaccination response | Induced response only | Vaccination response | Induced response only | Induced response only | |||
| 18 | Adjuvant | − | + | − | + | + | + | + | + | + | |
| 20 | Adjuvant | + | + | − | + | + | − | + | + | + | |
| 17 | CR* | − | + | − | − | + | + | − | − | + | |
| 9 | PR* | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 21 | SD* | − | − | − | − | − | − | − | − | − | |
| 11 | SD | + | − | + | + | + | − | + | − | − | |
| 12 | SD | − | + | − | − | + | + | − | − | + | |
| 25 | SD | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| 16 | PD | + | + | − | − | + | − | − | − | − | |
| 26 | PD | − | − | − | + | − | − | + | + | + | |
| 27 | PD | + | + | + | + | + | − | + | − | − | |
| Total | 4 | 6 | 2 | 5 | 7 | 3 | 5 | 3 | 5 | ||
Paired serial specimens were available in 11 patients. The top 2 lines represent the patients who received the vaccine as an adjuvant therapy for high-risk bladder cancer and did not recur during the study period. Patients are listed by the response types. Three patients with an asterisk (*) showed shrinkage of the tumors that lasted 24 weeks or longer when compared with the baseline sum of target lesions. Positive response was defined as the mean of the test specimen being greater than the control mean + 1 standard deviation. As there were baseline positive responses against HER2 as previously reported by other researchers, distinction was made in the right-side post-vaccination response summary columns marked “Induced response only” to denote when the baseline response (“Pre”) was absent and positive response was found only after the vaccination (“Post”) in at least one of the markers or the combinations tested. (A) Production of IFN-γ, granzyme B, and TNF-α by PBMCs stimulated by HER2 peptide mix. If there was a response in at least one of IFN-γ, granzyme B, or TNF-α, it was considered as having a positive post-vaccination response. Of the 11 patients tested, 7 developed responses against extracellular domain (ECD) and 7 developed responses against intracellular domain (ICD) of HER2. Combining the response against ECD and ICD, 10 patients (91%) among 11 showed newly induced anti-HER2 response. (B) Assessment of multifunctional T-cell response. The detection of simultaneous production in at least two of IFN-γ, granzyme B, or TNF-α in combination was considered a positive response. Of the 11 patients tested, 6 (55%) developed new multifunctional responses against ECD that were not present prior to vaccination and 6 (55%) showed newly detected multifunctional responses against ICD. Of note, ICD was not included in the transduced antigen when the AdHER2 DC vaccine was manufactured. Combining the response against ECD and ICD, 8 patients (72.7%) among 11 showed newly induced anti-HER2 cellular responses. Reviewed by the domains of induced responses, several of the patients with polyfunctional lymphocyte response had vaccine-induced responses in Table 5A (ECD 9, 12, 26, and 27; ICD 9, 18, 20, 26, and 27) and in the domains they showed polyfunctional responses. (C) Production of IL-4 by peripheral blood lymphocytes after AdHER2 DC vaccination. Production of IL-4 was checked as a surrogate marker of Th2 cell activity. Newly induced IL-4 production after the vaccination in both groups of cells stimulated by ECD and ICD HER2 peptide mix was noted.
GB, granzyme B; ECD, extracellular domain; ICD, intracellular domain; Pre, pre-vaccination; Post, post-vaccination; Adjuvant, bladder cancer adjuvant indication bladder cancer; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NA, not available.