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1857A
A Phase I Study Of HER-2/NEU (HER2)
Peptide-Based Vaccines For The Generation Of HER2 Specific Immunity
In Patients With HER2 Overexpressing Cancers M Disis, T .
Gooley, K Knuston, M Cheever, K Rinn, D Davis, K Schiffman, Univ of
Washington, Seattle, WA; Fred Hutchinson Cancer Research Center and
Corixa Corporation, Seattle, WA.
Patients with Stage III/IV HER2 overexpressing breast, ovarian,
or non-small cell lung cancers were immunized with HER2
peptide-based vaccines. Three vaccine formulations were tested, each
composed of 3 peptides derived from the HER2 protein sequence, and
each designed to elicit a helper T-cell response. Vaccines were
given interdermally and GM-CSF was used as a vaccine adjuvant. 64
patients were enrolled and immunized once a month for a total of 6
immunizations. 38 patients completed all 6 vaccines; median for the
study population as a whole was 3 vaccines. There was no significant
toxicity associated with the immunizations or with the generation of
a HER2 specific immune response. Overall, 78% (n=50) of patients
immunized developed significant T-cell immunity (S.I.>2) to HER2
peptides, range of S.I. 2-59. 62% of patients (n=40) developed
significant HER2 protein specific T-cell responses, an in
vitro surrogate of potential tumor response, range S.I. 2-31.
There was no difference in the immunogenicity of the three vaccine
formulations tested. The phenomenon of epitope spreading, developing
a T-cell response to epitopes not in the immunizing vaccine, was
observed in 76% of patients (n=42). For patients receiving peptides
derived from the extracellular domain portion of the protein, the
development of epitope spreading significantly correlated with the
generation of a HER2 protein specific T-cell response. In responding
patients, biopsies after peptide skin tests were placed, revealed a
marked CD3+, CD4+ T-cell infiltrate with an increase in local CD1a+
cells. Peptide-based vaccines were less effective at generating HER2
antibody immunity. 55% of patients developed HER2 peptide specific
antibodies, but only 20% of patients generated HER2 protein specific
antibody. Patients are in follow-up after completing immunization a
median of 11 months, range 9-28 months. Analysis of longitudinal
responses demonstrates that HER2 specific immunity persists and
continues to evolve and augment after immunizations have been
completed.
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