Combination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors.
Gilham, David E
Hawkins, Robert E
Stern, Peter L
AffiliationCancer Research U.K. Immunology Group, Paterson Institute for Cancer Research, University of Manchester and Christie Hospital National Health Service Trust, Manchester M20 4BX, UK.
MetadataShow full item record
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.
CitationCombination of vaccination and chimeric receptor expressing T cells provides improved active therapy of tumors. 2006, 177 (7):4288-98 J. Immunol.
JournalJournal of Immunology
- Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors.
- Authors: Mulryan K, Ryan MG, Myers KA, Shaw D, Wang W, Kingsman SM, Stern PL, Carroll MW
- Issue date: 2002 Oct
- Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines.
- Authors: Wang J, Saffold S, Cao X, Krauss J, Chen W
- Issue date: 1998 Nov 15
- Immunization with lentiviral vector-transduced dendritic cells induces strong and long-lasting T cell responses and therapeutic immunity.
- Authors: He Y, Zhang J, Mi Z, Robbins P, Falo LD Jr
- Issue date: 2005 Mar 15
- Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens.
- Authors: Kaplan JM, Yu Q, Piraino ST, Pennington SE, Shankara S, Woodworth LA, Roberts BL
- Issue date: 1999 Jul 15
- Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma.
- Authors: Pilon-Thomas S, Mackay A, Vohra N, Mulé JJ
- Issue date: 2010 Apr 1