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, Jahrgang 108, Nr. 2, 10.01.2004, S. 307-13.

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@article{8c71a117122a4b8db137732f253b2071,
title = "Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells",
abstract = "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.",
keywords = "Antibodies, Neoplasm, Antigens, Neoplasm, Cancer Vaccines, Cloning, Molecular, Cytotoxicity, Immunologic, DNA Primers, Gene Library, Genetic Therapy, Humans, Immunotherapy, Interleukin-12, Interleukin-7, Interleukins, Male, Melanoma, Reverse Transcriptase Polymerase Chain Reaction, Skin Neoplasms, Testis, Vaccination",
author = "Hanno Ehlken and Dirk Schadendorf and Stefan Eichm{\"u}ller",
note = "Copyright 2003 Wiley-Liss, Inc.",
year = "2004",
month = jan,
day = "10",
doi = "10.1002/ijc.11537",
language = "English",
volume = "108",
pages = "307--13",
journal = "INT J CANCER",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

RIS

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 -