Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells.
Although the existence of a humoral response against tumor-associated antigens is well appreciated, a systematic analysis of its possible induction by the tumor remains missing. We compared the specific IgG response of Stage IV melanoma patients during vaccination. Patients had been treated within 2 clinical trials with autologous tumor cells gene-modified for IL-7 or IL-12. A panel of 27 tumor-associated antigens (HD-MM-01 to HD-MM-27) was isolated by a SEREX screening of a testis cDNA library using a pool of 5 sera from patients after vaccination. All antigens were retested with individual sera of 12 patients both pre- and post-vaccination. A serological response was induced during vaccination against 18 antigens. Remarkably, induction was detected only in patients included in the screening pool. The low overlap between sero-reactivity of the 12 patients suggested a very individualized immunological reaction. Two of 5 sera included in the screening pool exhibited a high frequency of induced humoral responses. The same patients had been shown to have a high Karnovsky index and had generated lytic cytotoxic T cells against the tumor. Besides 2 known cancer-germline genes (SCP-1 and PLU-1), the other isolated antigens were expressed in a non-tumor-specific fashion as analyzed by virtual Northern blot or RT-PCR. The properties of homologues to several of the identified tumor-antigens, especially PLU-1, SCP-1, DNEL2, CLOCK, and PIASx-alpha, suggest further investigation of their possible function in malignant melanoma. We conclude that a strong humoral response against tumor-associated antigens is inducible by tumor cells and that this response is very individual.
Ehlken
Hanno
H
German Cancer Research Center (DKFZ), Skin Cancer Unit (D070), Heidelberg, Germany.
Schadendorf
Dirk
D
Eichmüller
Stefan
S
D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000737:chemistry; D015723:Gene Library; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000235:genetics; D015851:Interleukin-7 / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D013737:Testis / Q000378:metabolism; D014611:Vaccination
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017931:DNA Primers; D015851:Interleukin-7; D007378:Interleukins; D018664:Interleukin-12