Rebuttal from Authors re: Christian Doehn. Immunotherapy of Prostate Cancer. Eur Urol 2008;53:681–3 Andrea Kiessling a,b , Susanne Fu ¨ ssel c , Rebekka Wehner a , Michael Bachmann a , Manfred P. Wirth c , E. Peter Rieber a , Marc Schmitz a, * a Institute of Immunology, Medical Faculty, Technical University of Dresden, 01307 Dresden, Germany b Institute of Medical Immunology, Medical Faculty, Martin-Luther- University Halle-Wittenberg, 06112 Halle, Germany c Department of Urology, Medical Faculty, Technical University of Dresden, 01307 Dresden, Germany The absence of effective therapeutic strategies for patients with advanced prostate cancer (PCa) has entailed an intensive search for novel treatment modalities. Increasing knowledge of the mechan- isms governing specific immune reactions against tumor cells paved the way for the design of T-cell- and antibody-based immunotherapy for PCa as outlined in our review article [1]. Following the identification of tumor-associated antigens (TAAs), which are capable of activating tumor- reactive T cells, clinical trials enrolling men with PCa were conducted, based on dendritic cells (DCs) pulsed with TAA-derived peptides, proteins, or mRNA. Furthermore, patients with PCa were vacci- nated with TAAs, which may be processed and presented by DCs in vivo, resulting in an efficient stimulation of tumor-reactive T cells. These clinical trials revealed that T-cell–based immunotherapeu- tic strategies represent safe and feasible concepts for the induction of immunologic and clinical responses in men with PCa. The administration of TAA-specific monoclonal antibodies that exhibit their antitumor effects via antibody-dependent cellular cytotoxicity and complement activation or bispecific antibodies engaging immune effector cells into tumor eradication also resulted in some clinical responses in patients with PCa. Despite these promising effects of specific immunotherapy, the clinical efficiency for patients with advanced PCa is still limited. An improvement of current treatment concepts for advanced PCa may be achieved by combining specific immunotherapeutic strategies with che- motherapy or androgen-deprivation therapy as mentioned in our review and in the corresponding editorial [1,2]. Recent findings revealed that che- motherapeutic agents can efficiently stimulate antitumor immune responses by triggering immu- nogenic tumor cell death. Thus, chemotherapy- treated tumor cells can emit signals that promote their phagocytosis and the subsequent processing and presentation of TAAs by DCs leading to the induction of CD8 + cytotoxic T lymphocytes (CTLs) and CD4 + T cells. CD8 + CTLs destroy tumor cells, whereas CD4 + T cells directly or indirectly support the activation and expansion of tumor- reactive CD8 + CTLs. In this context, Obeid et al [3] have recently demonstrated that some chemother- apeutic agents induce the translocation of intracellular calreticulin to the surface of tumor cells. Surface-exposed calreticulin plays a crucial role for the phagocytosis of dying tumor cells by DCs, resulting in an effective antitumor immune response. In addition, Apetoh et al [4] have shown that chemotherapy-treated tumor cells release high-mobility-group box 1 protein that interacts with Toll-like receptor 4 (TLR-4) expressed by DCs. TLR-4 triggering essentially contributed to an efficient processing and presen- tation of antigens derived from dying tumor cells resulting in the induction of potent tumor- directed T-cell responses [4]. These and further findings, which have been stressed by Lake and Robinson [5], encourage the design of clinical trials combining specific immunotherapy with chemotherapy. Recently, a pilot clinical trial enrolling 28 patients with metastatic, androgen-independent PCa was conducted to investigate a combination of these therapeutic strategies [6]. Patients were treated either with vaccine alone or with a combination of the vaccine and the chemotherapeutic agent doc- etaxel, which was recently approved for this disease. The vaccination regimen was composed of an admixture of recombinant vaccinia virus (rV) expressing prostate-specific antigen (PSA) and rV expressing the T-cell costimulatory molecule B7.1/CD80 followed by booster vaccinations with recombinant fowlpox virus containing PSA. Vac- cine-induced PSA-specific T-cell responses were not inhibited by docetaxel. A decline in serum PSA was observed in 3 of 14 patients treated with vaccine alone, none over 50%. In the combination therapy arm, 6 of 14 patients had a decline in serum PSA, including 3 patients showing declines of >75%. Patients treated with the vaccine plus docetaxel had a median progression-free survival of 3.2 mo, whereas patients who received the DOIs of original articles: 10.1016/j.eururo.2007.11.043, 10.1016/j.eururo.2007.12.038 * Corresponding author. Institute of Immunology, Medical Faculty, Technical University of Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Tel. +49 351 4586501; Fax: +49 351 4586316. E-mail address: marc.schmitz@tu-dresden.de (M. Schmitz). european urology 53 (2008) 681–685 684