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. STUDY DESIGN: 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.
BACKGROUND: We have treated disease-free breast cancerpatients 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. STUDY DESIGN: Disease-free breast cancerpatients were enrolled after standard therapy in phase I/II trials. A3patients 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 A3patients 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 A3patients' 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-A3patients respond similarly to E75 vaccination as HLA-A2 patients, suggesting the potential use of the E75 vaccine in up to 76% of the population.
Authors: G Travis Clifton; Jennifer K Litton; Karen Arrington; Sathibalan Ponniah; Nuhad K Ibrahim; Victor Gall; Gheath Alatrash; George E Peoples; Elizabeth A Mittendorf Journal: Ann Surg Oncol Date: 2017-03-17 Impact factor: 5.344
Authors: Carlos L Arteaga; Mark X Sliwkowski; C Kent Osborne; Edith A Perez; Fabio Puglisi; Luca Gianni Journal: Nat Rev Clin Oncol Date: 2011-11-29 Impact factor: 66.675
Authors: Dmitri V Rozanov; Nikita D Rozanov; Kami E Chiotti; Ashok Reddy; Phillip A Wilmarth; Larry L David; Seung W Cha; Sunghee Woo; Pavel Pevzner; Vineet Bafna; Gregory G Burrows; Juha K Rantala; Trevor Levin; Pavana Anur; Katie Johnson-Camacho; Shaadi Tabatabaei; Daniel J Munson; Tullia C Bruno; Jill E Slansky; John W Kappler; Naoto Hirano; Sebastian Boegel; Bernard A Fox; Colt Egelston; Diana L Simons; Grecia Jimenez; Peter P Lee; Joe W Gray; Paul T Spellman Journal: J Proteomics Date: 2018-01-10 Impact factor: 4.044