Combination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72718
Title:
Combination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors.
Authors:
Jiang, Hui-Rong; Gilham, David E; Mulryan, Kate; Kirillova, Natalia; Hawkins, Robert E; Stern, Peter L
Abstract:
We have generated murine T cells expressing chimeric immune receptors (CR) against human 5T4 oncofetal Ag (h5T4) and evaluated their tumor therapeutic efficacy alone and in combination with immunization using a replication-defective adenovirus encoding h5T4 (Rad.h5T4) and bone marrow-derived dendritic cells (BMDC). The h5T4-specific engineered T cells demonstrated Ag-specific, non-MHC-restricted cytolysis of h5T4-positive B16 and CT26 tumor cells in vitro by cytotoxicity assay and antitumor activity in vivo using a Winn assay. In the s.c. injected B16h5T4 melanoma model, early local but not systemic i.v. administration of syngeneic h5T4-specific CR T cells significantly increased mice survival. This improvement was further enhanced when combined with immunization with Rad.h5T4, followed by post-CR T cell treatment with BMDC in the active therapy model, possibly through mechanisms of enhancing Ag-specific cellular immune responses. This synergistic effect was lost without delivery of the BMDC. Our findings suggest that combining engineered T cells with specific vaccination strategies can improve the active tumor therapy.
Affiliation:
Cancer Research U.K. Immunology Group, Paterson Institute for Cancer Research, University of Manchester and Christie Hospital National Health Service Trust, Manchester M20 4BX, UK.
Citation:
Combination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors. 2006, 177 (7):4288-98 J. Immunol.
Journal:
Journal of Immunology
Issue Date:
1-Oct-2006
URI:
http://hdl.handle.net/10541/72718
PubMed ID:
16982863
Type:
Article
Language:
en
ISSN:
0022-1767
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJiang, Hui-Rong-
dc.contributor.authorGilham, David E-
dc.contributor.authorMulryan, Kate-
dc.contributor.authorKirillova, Natalia-
dc.contributor.authorHawkins, Robert E-
dc.contributor.authorStern, Peter L-
dc.date.accessioned2009-07-07T10:49:02Z-
dc.date.available2009-07-07T10:49:02Z-
dc.date.issued2006-10-01-
dc.identifier.citationCombination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors. 2006, 177 (7):4288-98 J. Immunol.en
dc.identifier.issn0022-1767-
dc.identifier.pmid16982863-
dc.identifier.urihttp://hdl.handle.net/10541/72718-
dc.description.abstractWe have generated murine T cells expressing chimeric immune receptors (CR) against human 5T4 oncofetal Ag (h5T4) and evaluated their tumor therapeutic efficacy alone and in combination with immunization using a replication-defective adenovirus encoding h5T4 (Rad.h5T4) and bone marrow-derived dendritic cells (BMDC). The h5T4-specific engineered T cells demonstrated Ag-specific, non-MHC-restricted cytolysis of h5T4-positive B16 and CT26 tumor cells in vitro by cytotoxicity assay and antitumor activity in vivo using a Winn assay. In the s.c. injected B16h5T4 melanoma model, early local but not systemic i.v. administration of syngeneic h5T4-specific CR T cells significantly increased mice survival. This improvement was further enhanced when combined with immunization with Rad.h5T4, followed by post-CR T cell treatment with BMDC in the active therapy model, possibly through mechanisms of enhancing Ag-specific cellular immune responses. This synergistic effect was lost without delivery of the BMDC. Our findings suggest that combining engineered T cells with specific vaccination strategies can improve the active tumor therapy.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectCanceren
dc.subject.meshAdenoviridae-
dc.subject.meshAdoptive Transfer-
dc.subject.meshAnimals-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCancer Vaccines-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCombined Modality Therapy-
dc.subject.meshDendritic Cells-
dc.subject.meshFlow Cytometry-
dc.subject.meshGenetic Vectors-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshNeoplasms, Experimental-
dc.subject.meshReceptors, Antigen, T-Cell-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshT-Lymphocytes-
dc.subject.meshTransduction, Genetic-
dc.titleCombination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors.en
dc.typeArticleen
dc.contributor.departmentCancer Research U.K. Immunology Group, Paterson Institute for Cancer Research, University of Manchester and Christie Hospital National Health Service Trust, Manchester M20 4BX, UK.en
dc.identifier.journalJournal of Immunologyen

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