Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells:: Results of a Phase I clinical trial

被引:96
作者
Fuessel, Susanne
Meye, Axel
Schmitz, Marc
Zastrow, Stefan
Linne, Clemens
Richter, Katja
Loebel, Barbel
Hakenberg, Oliver W.
Hoelig, Kristina
Rieber, E. Peter
Wirth, Manfred P.
机构
[1] Tech Univ Dresden, Dept Urol, Fac Med, D-01307 Dresden, Germany
[2] Tech Univ Dresden, Fac Med, Inst Immunol, D-8027 Dresden, Germany
[3] Tech Univ Dresden, Fac Med, Inst Transfus Med, D-8027 Dresden, Germany
关键词
T-cell response; dendritic cells; ELISPOT assay; hormone-refractory prostate cancer; immunotherapy;
D O I
10.1002/pros.20404
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. Immunotherapies might represent promising alternatives for the treatment of patients with hormone-refractory prostate cancer (HRPC). In a Phase I clinical trial, we evaluated a vaccination with dendritic cells (DCs) loaded with a cocktail consisting of HLAA*0201-restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)]. METHODS. Eight HRPC patients received a total of four vaccinations every other week. Clinical and immunological responses were monitored by the determination of the serum PSA levels and by enzyme linked immunospot (ELISPOT) analyses, respectively. RESULTS. Apart from local skin reactions no side effects were noted. One patient displayed a partial response (PR; PSA decrease > 50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8(+) T-cell activation against prostein, survivin, and PSMA. CONCLUSIONS. The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa.
引用
收藏
页码:811 / 821
页数:11
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