Genetically modified tumour vaccines (GMTV) in melanoma clinical trials.
Since melanoma is a model immunogenic malignancy incurable in the disseminated phase of its natural course different immunotherapeutic approaches are tested in clinical trials. A number of tumour vaccines genetically modified (GMTV), with various immunostimulatory factors, are tested in phase I/II clinical trials. These factors include cytokines, tumour antigens (TA), costimulatory molecules or HLA antigens. We have designed a novel, mixed auto/allogeneic cellular melanoma vaccine modified with the IL-6 and the sIL-6R genes. Preclinical studies in a mouse model demonstrated that the IL-6/sIL-6R based vaccine is able to elicit efficient anti-tumour responses, mediated by CD8+ and NK cells, which resulted in inhibition of the tumour growth, metastases formation and prolonged survival of the animals treated. Irradiation of vaccine cells does not only lead to their sterilisation but also causes increased secretion of exogenous IL-6 and sIL-6R. Since January 1996 we have vaccinated more than one hundred metastatic melanoma patients. Promising clinical results (22% CR+PR, 32% SD) and the evidence of immune responses in the vaccinated patients have prompted us to design a phase III clinical trial which is to be open in 2000.
Nawrocki
S
S
Department of Radiation Oncology, Great Poland Cancer Centre, ul. Garbary 15, 61-866, Poznań, Poland.
Murawa
P
P
Malicki
J
J
Kapcinska
M
M
Gryska
K
K
Izycki
D
D
Kaczmarek
A
A
Laciak
M
M
Czapczyk
A
A
Karczewska
A
A
Rose-John
S
S
Mackiewicz
A
A
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000528:radiation effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005818:Genetic Engineering; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology; D012995:Solubility; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000528:radiation effects / Q000627:therapeutic use*
D019496:Cancer Vaccines; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014614:Vaccines, Synthetic