Anti-tumor immune responses and tumor regression induced with mimotopes of a tumor-associated T cell epitope.
Mimotopes provide an alternative to natural T cell epitopes for cancer immune therapy, as they can recruit and stimulate T cell repertoires that deviate from the repertoires engaged with the tumor and exposed to disease-related immune suppression. Here, mimotopes of a shared tumor-associated T cell epitope in cutaneous lymphoma were tested for their capacities to induce clinical and immunological responses in cancer patients. The mimotope sequences had been determined by a combinatorial peptide library approach without knowledge of the corresponding natural tumor-associated antigen. Vaccination with these mimotopes together with helper T cell-inducing antigens led to complete tumor remission in the two patients tested. After each booster vaccination, enhanced frequencies of mimotope-specific CD8+ T cells were detected in the peripheral blood of the patients, and the CTL proved to be cytotoxic and tumoricidal when tested in vitro. These data provide a first indication of clinical efficacy of mimotopes in cancer patients.
Department of Dermatology and Allergy, Charité--University Medicine Berlin, Humboldt University, Berlin, Germany.
Sherev
S
Tumenjargal
Sylke
S
Gellrich
Thomas
T
Linnemann
J Marcus
JM
Muche
Ansgar
A
Lukowsky
Heike
H
Audring
Karl-Heinz
KH
Wiesmüller
Wolfram
W
Sterry
Peter
P
Walden
D019496:Cancer Vaccines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012878:Skin Neoplasms / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte