Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells
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Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells. / Ehlken, Hanno; Schadendorf, Dirk; Eichmüller, Stefan.
In: INT J CANCER, Vol. 108, No. 2, 10.01.2004, p. 307-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells
AU - Ehlken, Hanno
AU - Schadendorf, Dirk
AU - Eichmüller, Stefan
N1 - Copyright 2003 Wiley-Liss, Inc.
PY - 2004/1/10
Y1 - 2004/1/10
N2 - 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.
AB - 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.
KW - Antibodies, Neoplasm
KW - Antigens, Neoplasm
KW - Cancer Vaccines
KW - Cloning, Molecular
KW - Cytotoxicity, Immunologic
KW - DNA Primers
KW - Gene Library
KW - Genetic Therapy
KW - Humans
KW - Immunotherapy
KW - Interleukin-12
KW - Interleukin-7
KW - Interleukins
KW - Male
KW - Melanoma
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Skin Neoplasms
KW - Testis
KW - Vaccination
U2 - 10.1002/ijc.11537
DO - 10.1002/ijc.11537
M3 - SCORING: Journal article
C2 - 14639620
VL - 108
SP - 307
EP - 313
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
ER -