Ulrich Keilholz

..18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations...

..This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma...

..Inconsistent reports on the detection of melanoma cells in peripheral blood by reverse transcriptase-PCR (RT-PCR) have resulted in uncertainty on the prognostic value of circulating melanoma cells...

..These results show that CXCR3 expression on vaccine-induced T cells can be modulated by modifying the local vaccine milieu...

....

..CONCLUSION: In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*01-restricted T cell epitope of the tumor antigen WT1, which is of considerable interest for use in vaccination trials...

..The aim of this study was to determine in patients with high-risk primary uveal melanoma whether the detection of circulating tumor cells by quantitative reverse transcription-PCR (RT-PCR) is of prognostic relevance...

..These effects are of relevance for tumor immunotherapy and provide a potential mechanism for the clinical efficacy of HDC added to IL-2...

..The findings reported here have implications for the development of antigen-specific T-cell therapies...

..Therefore, we asked whether sorafenib had an influence on peripheral immune effector cells in a cohort of 35 mRCC patients receiving sorafenib treatment...

..At the time of relapse, the same clone reappeared spontaneously in PB but not in BM showing impaired functionality...

..There is accumulating evidence from clinical cancer vaccination trials of a relation between the induction of specific T cells and clinical efficacy...

....

..Further studies would be necessary to identify a potential intracellular role of the truncated CCR7, abundantly present in the cytoplasm...

....

..CMV specific BM-derived T(CM) might be a valuable source for generating T cells for adoptive transfer...

..Although a proof for the clinical significance of EGFR-positive circulating tumor cells is currently lacking, expression of EGFR may predict response to lapatinib-based treatments as in the case presented...

..1% versus 47.3%, respectively. Based on the observation of prolonged disease stabilization, we recommend further investigation of the gemcitabine/treosulfan combination with a dose of 3500 mg/m2 of treosulfan in metastatic uveal melanoma...

..9-13.8). Grade 3 and 4 thrombopenia and leucopenia occurred in eight and nine of the 19 patients, respectively. The addition of cisplatin to the GeT regimen results in excessive haematological toxicity without improvement in efficacy...

..The positive prognostic influence of high TGF-?1 mRNA expression levels may reflect immune promoting functions of TGF-? in combined activity with inflammatory cytokines...

..This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment...

..It was unclear whether the similarities of the two drugs would lead to complete cross-resistance, or whether sequential application would be efficacious...

..These findings show that CMCs expressed stem cell-associated markers NES and CD133. Higher expression of NES on CMCs might represent an index of poor prognosis...

..Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation...

..TACE is well tolerated and effective in pretreated patients with liver metastases from uveal melanoma. TACE should further be evaluated as first-line therapy in prospective randomized clinical trials...

..These results suggest that peptide vaccination resulted in a prolonged relapse-free interval in these high-risk patients...

..The combined application of GM-CSF and KLH was associated with early induction of T-cell responses...

..Our results demonstrate the suitability of methylotrophic Pichia expression systems and laboratory-scale bioreactors for the production of high quantities of bifunctionally active heterologous single-chain fusion proteins...

..However, intracellular traffic and recycling to the cell surface appear to play a major role in its function and to have an influence on its surface density superseding translational regulation...

..Cox regression analysis, considering ALL phenotype as well as molecular-cytogenetic subsets, revealed no independent prognostic role of WT1 expression level for disease-free and overall survival...

..The association between aberrant expression of CXCR4 in the nucleus of non-small cell lung cancer and metastasis to lymph nodes points toward a potential tumor metastasis promoting function of nuclear CXCR4...

..A randomized phase II trial was conducted to determine if two non-platinum protocols are able to yield a similar efficacy and toxicity profile as compared to two platinum-based doublets in advanced non-small cell lung cancer (NSCLC)...

..Together, these findings support the potential of WT1 as a target for novel treatment approaches in AML...

..These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines...

..The efficacy and toxicity of bendamustine chemotherapy in relapsed small cell lung cancer (SCLC) was determined in this phase II trial...

..We conclude that either copy numbers of analyzed markers in circulating tumor cells are not sufficient for detection or, more probably, peripheral blood is not a suitable compartment for detection of tumor cells in colorectal cancer...

..This study suggests that peptide vaccination can generate a fully functional memory T-cell response characterized by central and effector memory phenotypes, proliferative potential, and BM tropism...

..To improve the tolerability and potential efficacy of this combination, the authors combined a moderate dose of continuous infusion ifosfamide with liposomal daunorubicin (L-Dauno)...

..The regulation of receptor function seems to be a critical step in the metastatic process...

..This study was undertaken to investigate the sensitivity of neoplastic B cells and solid tumor cells to proteasome inhibition with respect to constitutive expression levels of proteasome subunits...

..Extrapulmonary small cell carcinoma (EPSCC) is a rare disease of highly proliferating neuroendocrine tumor cells. Therapy and outcome of EPSCC patients treated at our institution were retrospectively analyzed...

..We optimized a method for enrichment, subsequent detection and characterization of CTCs based on depletion of the leukocyte fraction...

..According to Response Evaluation Criteria in Solid Tumours (RECIST), all patients showed progressive disease. We conclude that bendamustine is ineffective as second-line chemotherapy for metastatic uveal melanoma...

....

..Here, the heterogeneity of sequences within single families is the most challenging problem for exact quantification...

..In this study, we analyzed whether cetuximab-induced skin rash was correlated with distinct polymorphisms within the EGFR gene known to modulate EGFR expression, ligand binding, or signaling activity...

..Thus, the BM may be an important compartment for tumor surveillance harboring a tumor-specific memory T-cell pool in addition to effector T cells...

....

..Therefore current trials are under way trying to improve the efficacy of immunotherapy alone by adding histamine or vaccines to IL-2...

..However, PAX2 expression was frequently identified in neoplasia responsible for the growth and survival of cancer cells. Due to alternative splicing of exon 6, exon 10 and exon 12 four isoforms of PAX2 are described so far...

..In the uveal melanoma patients, one partial response (PR) and 15 stablisations of disease (SD) were recorded and whether this translates into a survival gain should be explored further...

..9, P<0.001) within the first 3 years. This study determined patients with ciliary body involvement to be candidates for future adjuvant therapeutic interventions...

....

..In this study, we address the question of whether this predominant clone or the accompanying V?11 restriction could be found in other AML patients vaccinated with the same WT1 peptide...

..Chemokine receptor CCR6 is expressed on a subset of T cells and is associated with their migration into the liver. This study was performed to analyze a possible association between CCR6 expressed by primary CRC and liver metastases...

..Both regimens were active with an overall response rate of 60% and 77%, respectively. The recommended dose of pegliposomal doxorubicin in the biweekly regimen for Phase II/III testing is 20 mg/m(2)...

....

..In two-thirds of leukaemias from our series, the basis of WT1 upregulation cannot be explained by the simple upregulation of the known WT1 activators...

..These results demonstrate bifunctional activity of the heterogeneous Pichia-produced A33scFv::CDy fusion protein and proof of principle for the ADEPT system proposed herein...

..No larger studies have performed a combined approach including WT1 mutation and expression analyses in acute T-lymphoblastic leukemia...

..Vinorelbine was added to carboplatin plus paclitaxel to determine efficacy and toxicity in non-small cell lung cancer (NSCLC) patients with good performance status...

....

..So far, none of the approaches has been proven to confer a survival benefit and thus the uniform desire is to include as many patients as possible in controlled clinical trials...

..Leukemic meningitis is a rare manifestation of CLL, especially in early stages. Selective spinal paraparesis as the first symptom of meningitis in CLL is even rarer and has been reported only once...

..This finding indicates that the T-cell response in regressing melanoma lesions is dominated by T cells directed toward a limited number of epitopes and that epitope-specific T cells frequently use a highly restricted TCR repertoire...

..To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients...

..Overall, these results provide the first evidence that a proportion of melanoma patients have circulating tumor-reactive T cells, which are lytic effectors cells...

..These results show that resistance to perforin-dependent pathways is not a relevant immune escape mechanism in lymphoma and therefore is unlikely to impair clinical outcome of immunotherapeutic approaches...

..In conclusion, adjuvant peptide vaccination was associated with cessation of recurrences in 4 of 9 patients, of whom all 4 had an immunologic response to the vaccine...

..In this study, we aimed to validate this finding in a large cohort of stage IV melanoma patients...

..The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs...

..Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually...

..v. infusion at a dose of 5mg/m(2), every 2 weeks, to patients with chemotherapy pretreated advanced non-small cell lung cancer (NSCLC)...

..In summary, our results demonstrate in principle the feasibility of A33-based enzyme targeting, but they call for small recombinant antibody-enzyme constructs to facilitate tumour penetration and clearance from the bloodstream...

..Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability...

..An urgent need for development of new treatment modalities is necessary and general principles of experimental immunotherapy are outlined...

..Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients...

..In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases...

Innovations and Challenges in Melanoma, chaired by Michael Atkins and cochaired by Ulrich Keilholz, John Kirkwood, and Jeffrey Sosman, was held July 15 to 16, 2005, in Cambridge, Massachusetts...

..This would provide a formidable tool for prognosis evaluation, anticancer-drug development and, ultimately, cancer-therapy personalization...