Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3102-3108
Author(s):  
Peter Brossart ◽  
Stefan Wirths ◽  
Gernot Stuhler ◽  
Volker L. Reichardt ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Tumor Antigen ◽  
Cytotoxic T Lymphocyte ◽  
B Cell Lymphoma ◽  
Breast And Ovarian Cancer ◽  
Her 2 ◽  
Single Tumor

Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu– or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-γ staining and 51Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu–derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.

Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3102-3108 ◽  
Author(s):  
Peter Brossart ◽  
Stefan Wirths ◽  
Gernot Stuhler ◽  
Volker L. Reichardt ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Tumor Antigen ◽  
Cytotoxic T Lymphocyte ◽  
B Cell Lymphoma ◽  
Breast And Ovarian Cancer ◽  
Her 2 ◽  
Single Tumor

Abstract Vaccination of patients with cancer using dendritic cells (DCs) was shown to be effective for B-cell lymphoma and malignant melanoma. Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu– or MUC1-derived peptides. Ten patients were included in this pilot study. The DC vaccinations were well tolerated with no side effects. In 5 of 10 patients, peptide-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood using both intracellular IFN-γ staining and 51Cr-release assays. The major CTL response in vivo was induced with the HER-2/neu–derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant. In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations. In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen. Our results show that vaccination of DCs pulsed with a single tumor antigen may induce immunologic responses in patients with breast and ovarian cancer. This study may be relevant to the design of future clinical trials of other peptide-based vaccines.

scholarly journals Cotransfection of dendritic cells with RNA coding for HER-2/neu and 4-1BBL increases the induction of tumor antigen specific cytotoxic T lymphocytes

2005 ◽  
Vol 12 (9) ◽  
pp. 749-756 ◽  
Author(s):  
Frank Grünebach ◽  
Katrin Kayser ◽  
Markus M Weck ◽  
Martin R Müller ◽  
Silke Appel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigen ◽  
Her 2

scholarly journals Lentiviral Transduction of Dendritic Cells Confers Protective Antiviral Immunity In Vivo

2004 ◽  
Vol 78 (14) ◽  
pp. 7843-7845 ◽  
Author(s):  
Shohreh Zarei ◽  
Shahnaz Abraham ◽  
Jean-Francois Arrighi ◽  
Olivier Haller ◽  
Thomas Calzascia ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Cytotoxic T Lymphocyte ◽  
Antiviral Immunity ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocyte Response ◽  
Vaccine Candidates ◽  
Virus Model ◽  
Cytotoxic T Lymphocyte Response

ABSTRACT Control of a viral infection in vivo requires a rapid and efficient cytotoxic-T-lymphocyte response. We demonstrate that lentivirus-mediated introduction of antigen in dendritic cells confers a protective antiviral immunity in vivo in a lymphocytic choriomeningitis virus model. Therefore, lentiviral vectors may be excellent vaccine candidates for viral infections.

scholarly journals In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is Cd4+ T Cell Independent

2000 ◽  
Vol 191 (2) ◽  
pp. 403-408 ◽  
Author(s):  
Qian Huang ◽  
Joan F.L. Richmond ◽  
Kimiko Suzue ◽  
Herman N. Eisen ◽  
Richard A. Young
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Fusion Proteins ◽  
Cytotoxic T Lymphocyte ◽  
Protein Domain ◽  
Cd4 T Cell ◽  
Fusion Partner

To gain insights into the mechanisms by which soluble heat shock protein (hsp) fusions can elicit CD8+ cytotoxic T lymphocytes (CTLs) against the fusion partner, mycobacterial (Mycobacterium tuberculosis) hsp70 was dissected to ascertain whether a particular hsp domain is necessary, and knockout mice were used to determine whether the fusion protein's immunogenicity is dependent on CD4+ T lymphocytes. We found that the ability to elicit CD8+ CTLs depends on a discrete 200–amino acid protein domain, indicating that the fusion protein's immunogenicity for CD8+ T cells does not require coupled chaperone function or peptide binding. Further, we found that ovalbumin (OVA).hsp70 fusion protein elicited anti-OVA CD8+ CTLs about equally well in CD4 knockout and wild-type C57BL/6 mice, and also when the hsp70 was of murine (self) origin. The ability of hsp70 fusion proteins to elicit CD4-independent CTL responses suggests that hsp70 fusion proteins may be useful for immunological prophylaxis and therapy against disease in CD4+ T cell–deficient individuals.

scholarly journals Cordyceps militaris Exerts Antitumor Effect on Carboplatin-Resistant Ovarian Cancer via Activation of ATF3/TP53 Signaling In Vitro and In Vivo

2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X2090255
Author(s):  
Eunbi Jo ◽  
Hyun-Jin Jang ◽  
Kyeong E. Yang ◽  
Min S. Jang ◽  
Yang H. Huh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
B Cell Lymphoma ◽  
Cordyceps Militaris ◽  
Exponential Growth Phase ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Parp 1

This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of carboplatin- resistant SKOV-3 and determine the underlying mechanisms for overcoming carboplatin resistance in human ovarian cancer. We cultured the carboplatin-resistant SKOV-3 cells in vitro until the exponential growth phase and then treated with different concentrations of C. militaris for 24, 48, and 72 hours. We performed cell proliferation assay, cell morphological change assessment using transmission electron microscopy, apoptosis assay, and immunoblotting to measure the protein expression of caspase-3 and -8, poly (ADP-ribose) polymerase (PARP)-1, B-cell lymphoma (Bcl)-2, and activating transcription factor 3 (ATF3)/TP53 signaling-related proteins. As a result, C. militaris reduced the viability of carboplatin-resistant SKOV-3 and induced morphological disruptions in a dose- and time-dependent manner. The gene expression profiles indicated a reprogramming pattern of the previously known and unknown genes and transcription factors associated with the action of TCTN3 on carboplatin-resistant SKOV-3 cells. We also confirmed the C. militaris-induced activation of the ATF3/TP53 pathway. Immunoblotting indicated that cotreatment of C. militaris and carboplatin-mediated ATF3/TP53 upregulation induced apoptosis in the carboplatin-resistant SKOV-3 cells, which are involved in the serial activation of pro-apoptotic proteins, including Bcl-2, Bax, caspases, and PARP-1. Further, when the ATF3 and TP53 expression increased, the CHOP and PUMA expressions were upregulated. Consequently, the upregulated CHOP/PUMA expression activated the positive regulation of the apoptotic signaling pathway. In addition, it decreased the Bcl-2 expression, leading to marked ovarian cancer cells sensitive to carboplatin by enhancing apoptosis. We then corroborated these results using in vivo experiments. Taken together, C. militaris inhibits carboplatin-resistant SKOV-3 cell proliferation and induces apoptosis possibly through ATF3/TP53 signaling upregulation and CHOP/PUMA activation. Therefore, our findings provide new insights into the treatment of carboplatin-resistant ovarian cancer using C. militaris.

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