Abstract
Conjugation of antigens to a carrier protein like keyhole limpet hemocyanin (KLH) has proven effective in clinical trials for inducing antibodies against selected tumor antigens. The impact of this approach on Tโcell immunity has not been previously tested. We utilized peripheral blood mononuclear cells (PBMC) obtained at leukapheresis from 6 breast cancer patients vaccinated 4 times each with a 106โamino acidโlong MUC1 peptide conjugated with KLH plus immune adjuvant QSโ21. Proliferation after 6 days of in vitro culture and an interferon gamma ELISPOT assay with and without 6 days of in vitro sensitization with the immunizing antigen were used. Parallel experiments employed the use of the cytokine IL2. Our results indicate that despite a high response to KLH in all patients with precursor frequencies as high as 1/120 peripheral blood lymphocytes and augmentation of proliferation in excess of 200โfold after vaccination, the Tโcell response against MUC1 peptide was minimal and inconsistent. The strength and consistency of the vaccineโinduced Tโcell response against KLH in these patients excludes general immune incompetence and assay insensitivity or inconsistency as explanations for the weak and inconsistent response against MUC1. We conclude that for any report of augmented Tโcell responses against MUC1 to be convincing, one or more postimmunization blood samples will be needed to demonstrate augmented MUC1โspecific immunity consistently on multiple occasions. Assuming this criteria, convincing induction of Tโcell immunity against MUC1 by vaccination has yet to be described. ยฉ 2001 WileyโLiss, Inc.