Humoral immune response against melanoma antigens induced by vaccination with cytokine gene‐modified autologous tumor cells

• Published in: International journal of cancer 2004-01, Vol.108 (2), p.307-313
• Main Authors: Ehlken, Hanno, Schadendorf, Dirk, Eichmüller, Stefan
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Neoplasm - blood; antibody response; Antigens, Neoplasm - immunology; Applied cell therapy and gene therapy; Biological and medical sciences; Cancer Vaccines - therapeutic use; Cloning, Molecular; Cytotoxicity, Immunologic; DNA Primers - chemistry; Gene Library; gene therapy; Genetic Therapy; Humans; immune response; Immunotherapy; Interleukin-12 - genetics; Interleukin-7 - genetics; Interleukins - genetics; Male; Medical sciences; Melanoma - immunology; Melanoma - therapy; Reverse Transcriptase Polymerase Chain Reaction; sero‐reactivity; Skin Neoplasms - immunology; Skin Neoplasms - therapy; Testis - metabolism; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; tumor antigens; Vaccination
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11537

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‐α, 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. © 2003 Wiley‐Liss, Inc.