Peptide-based cancer vaccines:adjuvant vaccination with melanoma peptide-pulsed dendritic cells (DCs) in stage III melanoma patients

• Autorzy: Markowicz S. , Nowecki Z.I. , Rutkowski P. , Lipkowski A.W. , Jakubowska-Mucka A. , Biernacka M. , Switaj T. , Misicka A. , Skurzak H. , Polowiniak-Pracka H. , Walewski J.A. , Ruka W.
• Języki publikacji: EN

Abstrakty

EN

Background: This is a pilot study evaluating of high-risk melanoma patients (pts) treated with peptide-DC vaccine after lymphadenectomy (LND). DC vaccination was designed to induce the immune response against melanoma antigens in melanoma pts who remain at high risk of dissemination after LND. Methods: DCs were generated from the bone marrow cultured with GM-CSF, SCF, FLT3-L and TNF-a or from peripheral blood adherent monocytes cultured with GM-CSF and IL-4. DCs pulsed with HLA-A2-binding TYR, MART-1 and gp100 peptides and/or HLAA1-binding MAGE-1, MAGE-3 peptides, tumor lysate if available, or with tracer antigen keyhole limpet hemocyanin (KLH), were injected subcutaneously 9 times within 8 months (mos). Boost injections were performed after 12 and 24 mos. Vaccinated pts were matched to unvaccinated controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, completion or therapeutic LND, Breslow stage (T), ulceration, and lactate dehydrogenase (LDH) level prior to LND. Results: HLA-A2+, -A1+ or -A3+ melanoma pts (n=22), stage III, N1b-N3, enrolled between Sept. 2002 and Apr. 2004, received 5-16 vaccinations (median: 11) within 2 yrs. Cutaneous delayed type hypersensitivity (DTH) to melanoma peptides was induced in 12 of 22 pts. Peptide-specific IFN-g; producing CD8+ cells were detected in peripheral blood of 13 of 19 pts after vaccination. At least one of these responses to melanoma antigens was elicited in 17 of 22 pts. DTH to KLH was positive in 15 of 22 pts. Eight vaccinated pts are free of disease (follow up is 77-97 mos after LND), and 1 in progression is lost from follow-up by Aug 30, 2010. Survival analysis of vaccinated pts and matched controls is presented in Table 1. Conclusions: The DC/peptide vaccine elicited immune responses to melanoma antigens. Vaccinated pts had clinically substantially longer overall survival (OS) and disease free survival (DFS) than matched control. OS was associated with the immune responsiveness to melanoma antigens and to KLH. Table 1: Survival analysis of vaccinated pts and matched controls. Vaccinated pts (n=22) 3-year OS [%]: 68.2 Matched control (n=22) 3-year OS [%]: 25.7 p-value accounting for matching 0.0290 HR (95% CI)* 3.25 (1.06-9.97) Vaccinated pts (n=19**) 3-year DFS [%]: 40.9 Matched control (n=22) 3-year DFS [%]: 14.5 p-value accounting for matching 0.1083 HR (95% CI)* 2.16 (0.82-5.7) *Cox Proportional Model - Hazard Ratio (HR) of unvaccinated pts **3 pts with recurrence before LND were excluded.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.156-157

Twórcy

autor

Markowicz S.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Nowecki Z.I.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Rutkowski P.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Lipkowski A.W.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Jakubowska-Mucka A.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Biernacka M.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Switaj T.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Misicka A.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Skurzak H.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Polowiniak-Pracka H.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Walewski J.A.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland

autor

Ruka W.

• Maria Sklodowska-Curie Memorial Institute-Cancer Centre, Warsaw, Poland