Clinical and immunologic responses of HLA-A3+ breast cancer patients vaccinated with the HER2/neu-derived peptide vaccine, E75, in a phase I/II clinical trial.
BACKGROUND
We have treated disease-free breast cancer patients with an HER2/neu-derived peptide, E75, as an adjuvant vaccine. E75 was originally described as HLA-A2-restricted and has been previously tested in this population. Based on computer modeling, E75 is predicted to bind to HLA-A3, and preclinical data support this. We conducted a clinical trial of E75 in HLA-A3(+), A2(-) (A3) patients.


METHODS
Disease-free breast cancer patients were enrolled after standard therapy in phase I/II trials. A3 patients were enrolled in parallel with A2 patients and vaccinated with E75 and granulocyte-macrophage colony-stimulating factor immunoadjuvant. A2(-), A3(-) patients were followed as controls. Toxicities were graded. Immunologic responses were assessed by delayed-type hypersensitivity reactions and E75-specific interferon-gamma enzyme-linked immunosorbent spot assay. Clinical recurrences were documented.


RESULTS
Thirteen A3 patients completed the vaccine schedule. Clinicopathologic features were similar between A3, A2, and control patients, except for more HER2/neu-overexpressing tumors in the A2 group and more estrogen-receptor/progesterone-receptor-negative tumors in A2 and A3 groups. Toxicity profiles and postvaccination delayed-type hypersensitivity were similar in A3 and A2 patients. Enzyme-linked immunosorbent spot assay results varied, but A3 patients' median spots increased pre- to postvaccination (p = 0.2). Recurrences were lower in the A3 group (7.7%) at 30-month median follow-up compared with published recurrence in A2-vaccinated (8.3%) and control groups (14.8%) at 26-month median follow-up.


CONCLUSIONS
HLA restriction limits potential use of peptide-based cancer vaccines. This trial demonstrates that HLA-A3 patients respond similarly to E75 vaccination as HLA-A2 patients, suggesting the potential use of the E75 vaccine in up to 76% of the population.
Patil
Ritesh
R
Joyce Murtha Breast Care Center, Windber Medical Center, Windber, PA, USA.
Clifton
Guy T
GT
Holmes
Jarrod P
JP
Amin
Asna
A
Carmichael
Mark G
MG
Gates
Jeremy D
JD
Benavides
Linda H
LH
Hueman
Matthew T
MT
Ponniah
Sathibalan
S
Peoples
George E
GE
D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines; D015331:Cohort Studies; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit
D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit; C474513:HER-2 peptide E75 (369-377), human