Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine.

Dangoor, A; Lorigan, P; Keilholz, U; Schadendorf, D; Harris, A; Ottensmeier, C; Smyth, J; Hoffmann, K; Anderson, R; Cripps, M; Schneider, J; Hawkins, R

Journal article

Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine.

Abstract:: BACKGROUND: Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes from five melanoma antigens. METHODS: Forty-one HLA-A2 positive patients with stage III/IV melanoma were enrolled. Patient groups received one or two doses of DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell responses were evaluated using ex-vivo tetramer and IFN-gamma ELISPOT assays. Safety and clinical responses were monitored. RESULTS: Prime-boost DNA/MVA induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31 (32%) patients. T cell responder rates were <50% with low-dose DNA/MVA, or MVA alone, rising to 91% with high-dose DNA/MVA. Among eight patients showing evidence of clinical benefit-one PR (24 months+), five SD (5 months+) and two mixed responses-seven had associated immune responses. Melan-A-tetramer+ immunity was associated with a median 8-week increase in time-to-progression (P = 0.037) and 71 week increase in survival (P = 0.0002) compared to non-immunity. High-dose vaccine was well tolerated. The only significant toxicities were flu-like symptoms and injection-site reactions. CONCLUSIONS: DNA.Mel3 and MVA.Mel3 in a prime-boost protocol generated high rates of immune response to melanoma antigen epitopes. The treatment was well tolerated and the correlation of immune responses with patient outcomes encourages further investigation.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Dangoor, A., Lorigan, P., Keilholz, U., Schadendorf, D., Harris, A., Ottensmeier, C., Smyth, J., Hoffmann, K., Anderson, R., Cripps, M., Schneider, J., & Hawkins, R. (2010). Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine. Cancer Immunology, Immunotherapy : CII, 59(6), 863–873.

MLA Style

Dangoor, A., et al. “Clinical and Immunological Responses in Metastatic Melanoma Patients Vaccinated with a High-Dose Poly-Epitope Vaccine.” Cancer Immunology, Immunotherapy : CII, vol. 59, no. 6, 2010, pp. 863–73.

Chicago Style

Dangoor, A, P Lorigan, U Keilholz, D Schadendorf, A Harris, C Ottensmeier, J Smyth, et al. 2010. “Clinical and Immunological Responses in Metastatic Melanoma Patients Vaccinated with a High-Dose Poly-Epitope Vaccine.” Cancer Immunology, Immunotherapy : CII 59 (6): 863–73.
Share
Print