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Tumor immunotherapy is currently at the cusp of becoming an important aspect of comprehensive cancer treatment in the clinic. However, the need for improved adjuvants to augment immune responses against tumor antigens is always present. In this paper, we characterize the Listeria monocytogenes-derived actin-nucleating protein, ActA, as a novel adjuvant for use in tumor immunotherapy. ActA is a virulence factor that is expressed on the cell surface of L. monocytogenes and facilitates the production of actin tails that propel Listeria throughout the cytosol of an infected host cell. It is believed that this ActA-dependent cytosolic motility allows Listeria to evade adaptive host cell defenses and facilitates its invasion into a proximal uninfected host cell. However, there is evidence that ActA fused to a tumor antigen and delivered by L. monocytogenes can perform a beneficial function in tumor immunotherapy as an adjuvant. Our investigation of this adjuvant activity demonstrates that ActA, either fused to or administered as a mixture with a tumor antigen, can augment anti-tumor immune responses, break immune tolerance and facilitate tumor eradication, which suggests that ActA is not only an effective adjuvant in tumor immunotherapy but can also be applied in a number of therapeutic settings. [ABSTRACT FROM AUTHOR]

In haematological cancers, malignant cells circulate in the blood and lymphatic system. This may make leukaemic cells easier to target by immunotherapy than in other types of cancer. Various immunotherapy strategies have been trialled in several leukaemias including chronic myeloid leukaemia (CML) and in general, these have been aimed at targeting tumour-associated antigens (TAA). There are numerous TAA expressed by CML patients including WT1, proteinase 3, BCR-ABL and HAGE amongst others. The immunogenicity of the CML-specific tumour antigen, BCR-ABL, has been the subject of much debate and its role in the development of the disease and its unique sequence spanning the breakpoint region make it an ideal target for immunotherapy. However, there are a limited number of immunogenic epitopes across the junctional region, which are restricted to only a few HLA types, namely A2, A3 and B7 (Clark et al. in Blood 98:2887–2893, ). The second CML-associated antigen is the helicase antigen HAGE, a cancer-testis antigen found to be over-expressed in more than 50% of myeloid leukaemias (Adams et al. in Leukaemia 16:2238–2242, ). Very little is known about the function of this antigen and its significance to CML. However, its membership of the DEAD-box family of ATP-dependent RNA helicases and the involvement of other members of this family in tumour cell proliferation (Eberle et al. in Br J Cancer 86:1957–1962, ; Yang et al. in Cell Signal 17:1495–504, ) suggest a crucial role in the RNA metabolism of tumour cells. For these reasons, HAGE also seems to be a good target for immunotherapy as it would be applicable for the majority of patients with CML. This review aims to discuss the potential of immunotherapy for the treatment of leukaemia, in particular CML, and the prospect of targeting three CML associated antigens: BCR, ABL and HAGE. During his career, Prof. Tony Dodi made a significant contribution in this area of leukaemia research, confirming the identity of immunogenic HLA-A3 and B7-restricted peptides as targets for CTL. Published, as a highlighted paper in Clark et al. (Blood 98:2887–2893, ), this study demonstrated the expression of MHC-peptide complexes on the surface of CML cells and the presence of tetramer-positive CTL activity in CML patients positive for these two HLA alleles. His drive and dedication for research excellence will be remembered by all who knew and worked with him. [ABSTRACT FROM AUTHOR]

The first analysis of our clinical trial on interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma was published in 2002 []. The aim of this paper is to update clinical results of 7 years of follow-up after the last treated patient. In the trial conducted between December 1993 and January 1999, patients without any detectable metastases after lymph node excision were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse-free interval was the primary objective. Eighty-eight patients were enrolled in the study. Currently, the last analysis performed in June 2006, after a median follow-up of 114.8 months, did not show change of non-significant extension of the relapse-free interval or overall survival. However, this second analysis strengthens our first hypothesis about the relationship between number of invaded lymph nodes and TIL treatment effectiveness. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P adjusted = 0.0219) and the overall survival was increased ( P adjusted = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either with regard to the duration of disease-free survival ( P adjusted = 0.38) or overall survival ( P adjusted = 0.43), were noted in the group with more than one invaded lymph node, whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study, with a very long follow up (median of almost 10 years), postulates for the first time relationship between TIL efficiency in stage III melanoma (AJCC) and number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the production of an effective in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Information about several papers discussed during the fourth international meeting of the Association for Immunotherapy of Cancer held in Germany is presented. Newly discovered tumor-associated antigens for antibody and T-cell based therapies were delivered and demonstrated. Various approaches and techniques targeting candidate antigens in immunotherapy were also discussed.