Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence.
AuthorsSmith, Caroline L
Dunbar, P Rod
Palmowski, Michael J
Gilbert, Sarah C
Hawkins, Robert E
Harris, Adrian L
AffiliationTumour Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, OX3 9DS, UK.
MetadataShow full item record
AbstractRecombinant plasmid DNA and attenuated poxviruses are under development as cancer and infectious disease vaccines. We present the results of a phase I clinical trial of recombinant plasmid DNA and modified vaccinia Ankara (MVA), both encoding 7 melanoma tumor antigen cytotoxic T lymphocyte (CTL) epitopes. HLA-A*0201-positive patients with surgically treated melanoma received either a "prime-boost" DNA/MVA or a homologous MVA-only regimen. Ex vivo tetramer analysis, performed at multiple time points, provided detailed kinetics of vaccine-driven CTL responses specific for the high-affinity melan-A(26-35) analogue epitope. Melan-A26-35-specific CTL were generated in 2/6 patients who received DNA/MVA (detectable only after the first MVA injection) and 4/7 patients who received MVA only. Ex vivo ELISPOT analysis and in vitro proliferation assays confirmed the effector function of these CTL. Responses were seen in smallpox-vaccinated as well as vaccinia-naive patients, as defined by anti-vaccinia antibody responses demonstrated by ELISA assay. The observations that 1) CTL responses were generated to only 1 of the recombinant epitopes and 2) that the magnitude of these responses (0.029-0.19% CD8(+) T cells) was below the levels usually seen in acute viral infections suggest that to ensure high numbers of CTL specific for multiple recombinant epitopes, a deeper understanding of the interplay between CTL responses specific for the viral vector and recombinant epitopes is required.
CitationRecombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. 2005, 113 (2):259-66 Int. J. Cancer
JournalInternational Journal of Cancer
- Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine.
- Authors: Dangoor A, Lorigan P, Keilholz U, Schadendorf D, Harris A, Ottensmeier C, Smyth J, Hoffmann K, Anderson R, Cripps M, Schneider J, Hawkins R
- Issue date: 2010 Jun
- Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara.
- Authors: Smith CL, Mirza F, Pasquetto V, Tscharke DC, Palmowski MJ, Dunbar PR, Sette A, Harris AL, Cerundolo V
- Issue date: 2005 Dec 15
- Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen.
- Authors: Allen TM, Vogel TU, Fuller DH, Mothé BR, Steffen S, Boyson JE, Shipley T, Fuller J, Hanke T, Sette A, Altman JD, Moss B, McMichael AJ, Watkins DI
- Issue date: 2000 May 1
- Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients.
- Authors: Zajac P, Oertli D, Marti W, Adamina M, Bolli M, Guller U, Noppen C, Padovan E, Schultz-Thater E, Heberer M, Spagnoli G
- Issue date: 2003 Nov 1
- Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo.
- Authors: Oertli D, Marti WR, Zajac P, Noppen C, Kocher T, Padovan E, Adamina M, Schumacher R, Harder F, Heberer M, Spagnoli GC
- Issue date: 2002 Mar 1