|
1856
Delayed Type Hypersensitivity (DTH) Response Is
a Predictor of Peripheral Blood T Cell Immunity After HER2 Peptide
Immunization. Kathy S. Schiffman, Kristine J. Rinn, Theodore
A. Gooley, Mary L. Disis, Univ of Washington, Seattle, WA; Fred
Hutchinson Cancer Research Ctr, Seattle, WA.
There are no standard methods for evaluating the generation of
tumor-specific immune responses after immunization with a cancer
vaccine. Borrowing from infectious disease models, a DTH response to
an antigenic challenge is widely used; however,
tumor-antigen-specific DTH responses have never been correlated to
in vitro measurements of T cell responses. 32 patients with
stage III or IV breast, ovarian, or non-small cell lung cancer
received immunizations monthly for 6 months with 1 of 3 HER2
peptide-based vaccine formulations admixed with GM-CSF as an
adjuvant. 30 days following their last immunization, subjects were
evaluated for DTH responses to the individual peptides in their
vaccine by placing each peptide intradermally at a site distant to
their vaccination site. Responses were measured for induration at 48
hours. Antigen-specific T-cell proliferative responses from
peripheral blood lymphocytes isolated at the time of peptide skin
test placement were measured and expressed as a stimulation index
(SI). HER2 peptide-specific DTH responses ³10-mm correlate significantly to a measurable
peptide-specific peripheral blood T cell response defined as S.I.
> 2.0 (p=0.0006). However, antigen-specific DTH responses with
magnitude between 5-9-mm were not significantly associated with the
development of systemic immunity. DTH 5-9-mm carried an odds ratio
of 1.3 (p=0.61) in predicting a measurable systemic tumor antigen
response. 28 responses to the 93 DTH tests placed measured ³10 mm. Of those, 21 were biopsied with 16
showing marked CD4+, CD3+ infiltrating cells. Findings presented
here demonstrate that tumor-antigen-specific DTH responses ³10-mm correlate with measurable in vitro
antigen-specific lymphocytic proliferation and are, in this model
system, a reflection of systemic immunization.
|
