Our findings suggest that synthetic TARP peptides, such as TARP(P5L)(4-13), may play a role in prostate and breast cancer immunotherapy.

No abstract

Summary. Cytomegalovirus (CMV) infection is a dangerous complication in immunosuppressed individuals such as allogeneic stem cell transplant patients. CMV disease can be prevented by the early post-transplant transfer of donorderived, CMV-directed, T cells. Fast and cost efficient methods to generate CMV-specific T cells are, therefore, warranted. The current study utilized peptide-pulsed and adenovirus-transduced dendritic cells (DC) to generate CMV-restricted T cells. After one stimulation with CMV pp65 495)503 peptide-pulsed DC and three re-stimulations with peptide-pulsed monocytes, virtually all T cells were CD8 + , expressed the relevant T cell receptor and exhibited high peptide-specific lytic activity. After only one stimulation, pp65 495)503 -restricted T cells could be sorted to a purity of higher than 95% and expanded up to 1000-fold in 2 weeks. This technique may prove useful for the rapid generation of large quantities of specific cytolytic T lymphocytes (CTL) for cell therapy. DC transduced with an adenoviral vector encoding the full-length pp65 protein (Adpp65) were able to simultaneously expand CTL against multiple epitopes of pp65. In addition, they activated CMVspecific CD4 + T-helper cells. This approach would stimulate multiple-epitope populations of pp65-specific T cells and could be made available to patients of any human leucocyte antigen (HLA) haplotype. DC transduced with adenoviral vectors to express full-length antigens may prove to be potent vaccines against viral pathogens and cancer.

1 The thymoleptic drug citalopram (CIT) belongs to the selective serotonin reuptake inhibitors (SSRIs) and is today extensively used in psychiatry. Further clari®cation of the enantiomer-selective distribution of racemic CIT in both clinical and toxic doses is highly warranted. 2 By a steady-state in vivo paradigm, rats underwent chronic systemic exposure for 10 days by using osmotic pumps and the total as well as the individual distributions of the S-and Renantiomers of CIT, and its metabolites in serum and two di erent brain regions, were analysed. 3 In serum, the S/R ratios in the groups treated with 10, 20, or 100 mg kg 71 day 71 were 0.94, 0.83, and 0.34, respectively. The ratios were almost the same in the brain regions. 4 In the group treated with 100 mg kg 71 day 71 , the serum and brain total CIT levels were found to be 20 times and 6 ± 8 times higher than in the rats treated with 10 or 20 mg kg 71 day 71 , respectively. In all groups, the CIT levels were higher in brain tissue as compared to serum. 5 In a spontaneous open-®eld behavioural test, a correlation between clinical and toxic drug concentrations was observed. 6 In conclusion, the R-enantiomer was present in an increased proportion compared with the Senantiomer when higher steady-state CIT concentration was prevailing. This is of particular interest, since the S-enantiomer is responsible for the inhibition of serotonin reuptake in vitro. The present data may be of importance, as full understanding on where di erent racemic or enantiomeric drug e ects of CIT and its main metabolites are unravelled.

Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.