Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy

Gonzalez, Gabriela; Crombet, Tania; Torres, F.; Catala, Mauricio; Alfonso, Lloyd F.; Osorio, Marta; Neninger, Elia; García, Beatriz; Mulet, A. Obrador; Pérez, Rolando; Lage, Ricardo da Cruz

doi:10.1093/annonc/mdg102

Cited by 108 publications

(83 citation statements)

References 11 publications

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“…Harvested cells were Ͼ90% DC as assessed by morphology and surface expression of CD13, CD33, CD54, CD80, CD86, and MHC classes I and II as well as expression of the DC marker CD83 upon maturation with CD40 ligand. Adenovirus infection of DC 6 and peptide loading of DC (17) were performed essentially as previously described.…”

Section: Generation and Ag Loading Of DCmentioning

confidence: 99%

“…6 After a total of four stimulations, cultures were tested for SOX-4-specific activity using IFN-␥ ELISPOT assays. SOX-4-specific T cell lines were cloned using anti-CD3 essentially as previously described.…”

Section: In Vitro Stimulation Of T Cellsmentioning

confidence: 99%

“…SOX-4-specific T cell lines were cloned using anti-CD3 essentially as previously described. 6 For CD4 T cells, in vitro stimulation cultures were established essentially as described previously (17). DC were pulsed with two pools of 42 SOX-4-derived 20-mer peptides overlapping by 15 aa, at a concentration of 250 ng/ml of each peptide.…”

Section: In Vitro Stimulation Of T Cellsmentioning

confidence: 99%

“…For IFN-␥ ELISPOT assays, IFN-␥ production by CD8 ϩ T cells was detected essentially according to published protocols, 6 using multiscreen 96-well filtration plates (MAIPS45; Millipore, Bedford, MA) coated with 10 g/ml IFN-␥ capture Ab (1DK1; Mabtech, Nacka, Sweden). ELISPOT plates were read using an ELISPOT counter (Zeiss, New York, NY).…”

Section: T Cell Assaysmentioning

confidence: 99%

“…To date, relatively few molecules have been identified that could be considered vaccine candidates for the treatment of lung cancer (5)(6)(7)(8)(9)(10). In most cases these molecules are expressed by either SCLC or NCSLC, but due to the differences in the cellular origin of these tumors, are not expressed by both lung cancer types.…”

mentioning

confidence: 99%

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Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

Friedman

Bangur

Zasloff

et al. 2004

The Journal of Immunology

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The developmental transcription factor SOX-4 has been shown to be highly and differentially overexpressed in primary small cell lung carcinomas (SCLC). To examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous, and large cell tumor samples as well as in a panel of established small cell and non-small cell lung carcinoma tumor cell lines. SOX-4 mRNA is shown to be overexpressed in a substantial fraction of each of these lung tumor types. To examine the immunological potential of SOX-4, we have evaluated the presence of SOX-4-specific CD4 and CD8 T cells in PBMC of healthy donors and the presence of SOX4-specific Abs in sera from SCLC patients. We demonstrate the presence of both CD4 and CD8 T cells that recognize naturally processed epitopes derived from SOX-4 as well as the presence of SOX-4-specific Abs in sera from SCLC patients, but not in sera from healthy donors. The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer. Furthermore, the identification of naturally processed T cell and Ab epitopes from SOX-4 provides valuable tools for the development of peptide-based vaccination strategies against lung cancer as well as to monitor SOX-4-specific responses in vaccinated patients.

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Section: Generation and Ag Loading Of DCmentioning

confidence: 99%

Section: In Vitro Stimulation Of T Cellsmentioning

confidence: 99%

Section: In Vitro Stimulation Of T Cellsmentioning

confidence: 99%

Section: T Cell Assaysmentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

Friedman

Bangur

Zasloff

et al. 2004

The Journal of Immunology

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Immunologic Approaches to Lung Cancer Therapy

Lee¹,

Dubinett²,

Sharma³

2008

Lung Cancer

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Induction of an antigen specific humoral immune response by immunization with the aggregate‐free human TGFα‐P64k fusion protein

Capote

Pérez

Hidalgo

et al. 2008

Drug Development Research

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Transforming growth factor alpha (TGFa) is an important epidermal growth factor receptor (EGFR) ligand. Over-expression of both molecules in epithelial tumors has been correlated with poor prognosis and disease progression. Due to the importance of TGFa in tumorigenesis, this molecule has great potential for cancer immunotherapy. We previously designed a TGFa-based vaccine consisting of a fusion protein between human TGFa (hTGFa) and P64k protein from Neisseria meningitidis expressed in Escherichia coli. However, this protein was obtained highly aggregated, which hampered its introduction into clinical use. In this study, we demonstrate that this aggregation state is not a consequence of IMAC purification, but is formed after bacterial disruption. To obtain this protein as a monomer, we designed a procedure that included an unfolding/refolding step at the end of purification. We verified that hTGFa in the refolded fusion protein (hTGFa-P64k-r) is immunogenic in mice. The latter was capable of inducing a humoral immune response against hTGFa identical to that generated with the aggregated fusion protein, demonstrating that the aggregation level has no influence on hTGFa immunogenicity. We also showed that TGFa-directed antibodies induced apoptosis in A431 cells. The present results also validated the potential use of this vaccine in cancer patients with tumors overexpressing TGFa. Drug Dev Res 69 : 481-494, 2008.

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Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy

Abstract: Vaccination with five doses of EGF vaccine is safe and immunogenic. Montanide ISA 51 increased the percentage of GAR. There is a direct relationship between anti-EGF antibody titers and immune response duration with survival time.

Cited by 108 publications

References 11 publications

Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

Immunologic Approaches to Lung Cancer Therapy

Induction of an antigen specific humoral immune response by immunization with the aggregate‐free human TGFα‐P64k fusion protein

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