title: Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC1.
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 T-cell 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 106-amino acid-long MUC1 peptide conjugated with KLH plus immune adjuvant QS-21. 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 200-fold after vaccination, the T-cell response against MUC1 peptide was minimal and inconsistent. The strength and consistency of the vaccine-induced T-cell 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 T-cell responses against MUC1 to be convincing, one or more postimmunization blood samples will be needed to demonstrate augmented MUC1-specific immunity consistently on multiple occasions. Assuming this criteria, convincing induction of T-cell immunity against MUC1 by vaccination has yet to be described.
authors.affiliation: Clinical Immunology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Musselli
authors.forename: Govindaswami
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Teresa
authors.initials: T
authors.lastname: Gilewski
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Yael
authors.initials: Y
authors.lastname: Spinat
authors.forename: Philip O
authors.initials: PO
authors.lastname: Livingston
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006433:Hemocyanins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology; D016233:Immunotherapy, Active; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D012503:Saponins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D000939:Epitopes; D018796:Immunoconjugates; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D012503:Saponins; C078785:saponin QA-21V1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin