Background: E75 (aa:369-377) and GP2 (aa:654-662) are HLA-A2-restricted peptides derived from HER2/neu that have been tested as vaccines in clinically disease-free breast cancer (BCa) patients in the adjuvant setting. We previously reported that E75 is safe and produces a similar immunologic response in HLA-A3 (A3) patients as well as HLA-A2 (A2) patients. Here we report that A3 patients experience epitope spreading to GP2 in response to E75 vaccination and that immunity to both peptides wanes over time but responds to boosting. Methods: Disease-free node-positive and node-negative A3 BCa patients were enrolled in phase I trials after completion of standard chemo/radiation therapy and vaccinated with E75 with GM-CSF immunoadjuvant monthly 4 or 6 times. Patients were offered a booster inoculation of E75 6 months after completing the primary series and every 6 months thereafter. Vaccine response was assessed ex-vivo by E75 and GP2-specific IFN-\#947; ELISPOT assay pre-vaccination (R0), prior to inoculation at one month intervals (R1-R5), one month (R6), and 6 months (RC6) after completing vaccination and before and after each booster. Results: Thirteen A3 patients have completed the primary vaccination series. The E75-specific IFN-\#947;-spot-forming cells (I-SFC) increased from a median of 7 to 13 I-SFC/10^6 cells pre- to post-vaccination (p=0.33). GP2-specific I-SFC increased from a median of 3 to 39 I-SFC /10^6 cells pre- to post-vaccination (p=0.001). At 6 months after completion of vaccination 62.5% (5/8) had residual immunity defined as > 0 E75-specific I-SFC /10^6 cells. This decreased to 37.5% (3/8) by the first booster inoculation at a median of 13 months. With boosting the residual immunity increased to 57% (4/7). GP2-specific immunity also waned but responded to boosting from a median of 14 to 62 GP2-specific I-SFC pre- to post booster. Conclusion: The HLA-A2-restricted peptide E75 is safe in A3 patients and generates E75-specific immunity. Our data demonstrates that E75 creates epitope spreading in A3 patients to HLA-A2-restricted GP2. The E75 and GP2-specific immunity wane with time but responds to boosting.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 720.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO