DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance
Authors: Chaise, C. et al.
Journal: Blood
Volume: 112
Issue: 7
Pages: 2956-2964
eISSN: 1528-0020
ISSN: 0006-4971
DOI: 10.1182/blood-2008-02-137695
Abstract:The Wilms tumor antigen, WT1, is associated with several human cancers, including leukemia. We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p. DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class l-binding epitope downstream of a foreign sequence of tetanus toxin. Three p. DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2-restricted epitope, induced cytotoxic T lymphocytes (CTLs) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTLs killed human leukemia cells in vitro, indicating peptide processing/presentation. Low numbers of T cells specific for these epitopes have been described in cancer patients. Expanded human T cells specific for each epitope were lytic in vitro. Focusing on human WT137-45-specific cells, the most avid of the murine responses, we demonstrated lysis of primary leukemias, underscoring their clinical relevance. Finally, we showed that these human CTL kill target cells transfected with the relevant p. DOM-peptide DNA vaccine, confirming that WT1-derived epitopes are presented to T cells similarly by tumors and following DNA vaccination. Together, these data link mouse and human studies to suggest that rationally designed DNA vaccines encoding WT1-derived epitopes, particularly WT137-45, have the potential to induce/expand functional tumor-specific cytotoxic responses in cancer patients. © 2008 by The American Society of Hematology.
Source: Scopus
DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance.
Authors: Chaise, C. et al.
Journal: Blood
Volume: 112
Issue: 7
Pages: 2956-2964
eISSN: 1528-0020
DOI: 10.1182/blood-2008-02-137695
Abstract:The Wilms tumor antigen, WT1, is associated with several human cancers, including leukemia. We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I-binding epitope downstream of a foreign sequence of tetanus toxin. Three p.DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2-restricted epitope, induced cytotoxic T lymphocytes (CTLs) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTLs killed human leukemia cells in vitro, indicating peptide processing/presentation. Low numbers of T cells specific for these epitopes have been described in cancer patients. Expanded human T cells specific for each epitope were lytic in vitro. Focusing on human WT1(37-45)-specific cells, the most avid of the murine responses, we demonstrated lysis of primary leukemias, underscoring their clinical relevance. Finally, we showed that these human CTL kill target cells transfected with the relevant p.DOM-peptide DNA vaccine, confirming that WT1-derived epitopes are presented to T cells similarly by tumors and following DNA vaccination. Together, these data link mouse and human studies to suggest that rationally designed DNA vaccines encoding WT1-derived epitopes, particularly WT1(37-45), have the potential to induce/expand functional tumor-specific cytotoxic responses in cancer patients.
Source: PubMed
DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance
Authors: Chaise, C. et al.
Journal: BLOOD
Volume: 112
Issue: 7
Pages: 2956-2964
eISSN: 1528-0020
ISSN: 0006-4971
DOI: 10.1182/blood-2008-02-137695
Source: Web of Science (Lite)
DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance.
Authors: Chaise, C. et al.
Journal: Blood
Volume: 112
Issue: 7
Pages: 2956-2964
eISSN: 1528-0020
ISSN: 0006-4971
DOI: 10.1182/blood-2008-02-137695
Abstract:The Wilms tumor antigen, WT1, is associated with several human cancers, including leukemia. We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I-binding epitope downstream of a foreign sequence of tetanus toxin. Three p.DOM-peptide vaccines, each encoding a different WT1-derived, HLA-A2-restricted epitope, induced cytotoxic T lymphocytes (CTLs) in humanized transgenic mice expressing chimeric HLA-A2, without affecting hematopoietic stem cells. Mouse CTLs killed human leukemia cells in vitro, indicating peptide processing/presentation. Low numbers of T cells specific for these epitopes have been described in cancer patients. Expanded human T cells specific for each epitope were lytic in vitro. Focusing on human WT1(37-45)-specific cells, the most avid of the murine responses, we demonstrated lysis of primary leukemias, underscoring their clinical relevance. Finally, we showed that these human CTL kill target cells transfected with the relevant p.DOM-peptide DNA vaccine, confirming that WT1-derived epitopes are presented to T cells similarly by tumors and following DNA vaccination. Together, these data link mouse and human studies to suggest that rationally designed DNA vaccines encoding WT1-derived epitopes, particularly WT1(37-45), have the potential to induce/expand functional tumor-specific cytotoxic responses in cancer patients.
Source: Europe PubMed Central