Journal of Immunotherapy:
In the abstract that appeared in Volume 27, Number 6, page S24, entitled Enhanced TH-1 Responses by Novel Ii-Key HER2/neu Peptides in Breast Cancer Patients, J Immunother. 2004;27:S1–S61, there were several errors.
The corrected abstract appears below.
Enhanced TH-1 Responses by Novel Ii-Key HER2/neu Peptides in Breast Cancer Patients
Kouichiro Kawano1, Clay Efferson1, Constantin G. Ioannides1, Robert E. Humphreys2, James Murray3. 1Laboratory of Vaccine Research, Gynecologic Oncology,2Antigen Express, Inc., Worchester, MA and3Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX.
Combinations of HER2/neu-derived MHC class I or class II restricted peptide vaccines have shown promise in treating breast cancer (BC). Preclinical studies demonstrate that improving the activity of Th1 “helper” epitopes can significantly enhance the strength of specific CTL responses against tumor Ag. Antigen Express has developed novel Ii-Key class II HER2 epitope vaccine peptides which contain an amino acid chain (LMRK-ava) which binds to a site outside the antigenic peptide groove of class II molecules and facilitates charging of the tethered epitope. We examined the ability of these Ii-Key peptides to enhance IFNγ secretion from peripheral blood mononuclear cells (PBMC) from early stage BC patients compared to PBMC stimulated in vitro with epitope-only peptides G89 or AE36. PBMC stimulated with Ii-Key peptides AE36-AE48 (table) had a 5-20 fold increase in IFNγ as measured by ELISA compared to G89. Two peptides, AE37 and AE47, induced greater frequency of positive responses than the other peptides in 5 of 9 patients tested. Similar results were observed using ELISPOT. Both AE37 and AE47 when combined as individual peptides with class I HER2 peptide E75 were synergistic in promoting IFNγ secretion compared to that produced in the presence of each individual peptide alone. In one patient an increase in IFNγ following AE37 stimulation was associated with a greater percentage of CD25+lo and a decrease in CD25+hi regulatory T cells compared to peptides which did not induce significant responses. These data demonstrate that novel Ii-Key HER2/neu class II peptides can induce enhanced in vitro Th1 responses as well as increase the strength of CTL epitope response of BC patient lymphocytes compared to wild type class I or class II epitope-only peptides. Hence, novel class II Ii-Key peptide hybrids combined with class I peptides might be more effective vaccines for increasing Th1 and CTL peptide-specific immune responses in patients. Supported in part by Grant DOD-1-299 (CGI) and funds from AE.Inc. (REH, EvH, KK).