Combination of high-dose chemotherapy and monoclonal antibody in breast-cancer patients: a pilot trial to monitor treatment effects on disseminated tumor cells.

BACKGROUND: Tumor relapse occurring in high-risk breast cancer patients after high-dose chemotherapy (HDC) and autologous stem-cell transplantation may arise from cells resistant to chemotherapy, as well as from tumor cells reinfused with autologous stem cell grafts. This pilot study was designed to investigate whether ex vivo immunomagnetic purging of PBSC and subsequent immunotherapy with MAb 17-1A is feasible and can reduce the number of disseminated tumor cells in BM. METHODS: Twelve high-risk breast-cancer patients, seven in Stage II/III and five in Stage IV (UICC breast cancer classification) underwent surgery of the primary tumor and received two cycles of induction chemotherapy, followed by HDC. After each cycle of induction chemotherapy PBSC were collected and incubated with Ab-coated immunomagnetic beads, to remove contaminating tumor cells. Prepared stem-cell grafts were transplanted 24 h after completion of HDC. After recovering from HDC all 12 patients received a total dose of 900 mg MAb 17-1A within 4 months. The effect of in vivo purging with MAb 17-1A after HDC was controlled by examining bone aspirates of the patients with an immunocytochemical assay, allowing the detection of one cytokeratin-positive tumor cell in 10(6) total nucleated cells (TNC). RESULTS: Tumor cells were found in 5/12 BM aspirates prior to chemotherapy and even after HDC. Further monitoring of BM aspirates for cancer cells during Ab therapy showed a consistent reduction of tumor cells in four out of these five patients. After a median clinical follow-up of 41 (32-48) months all four patients are alive. These results are different from those of a historical control group of six patients with breast cancer treated with the same chemotherapy schedule, but without 17/1A consolidation. In comparison with the patients from the study group, all patients of this control group revealed a significantly increased number of tumor cells in BM (p < 0.01) after HDC during follow-up of 5 (3-7) months. These preliminary results indicate that induction chemotherapy, followed by HDC, may reduce disseminated tumor cells in BM. DISCUSSION: Immunotherapy with MAb 17-1A after HDC may further eliminate residual disease without severe toxicity.

Autoreactive human T cell lines recognizing ribosomal protein L7.

Sera of patients suffering from systemic lupus erythematosus (SLE) frequently contain oligoclonal IgG autoantibodies with high affinity for the ribosomal protein L7 (rpL7). The humoral autoimmune response to rpL7 apparently is driven by antigen and T cell dependent. In order to analyze the T cell response to rpL7 we cultured peripheral blood lymphocytes of healthy individuals and SLE patients in the presence of recombinant rpL7. After 10 days, the cytokine response to re-stimulation with rpL7 was examined using a spot-ELISA. Measuring IFN-gamma secretion, the T cells of two patients and four healthy donors showed a significant increase in the number of spots as compared to control cells. Secretion of IL-4 or IL-10 was not detected. From the antigen-stimulated primary cultures we established by limiting dilution cloning six rpL7-reactive, IFN-gamma-secreting T cell lines which show a CD3+CD4+CD8- phenotype. One line additionally was shown to be positive for HLA-DR and CD45R0, but negative for CD27 and CD31. The cell lines carry alphabeta TCR chains which differ from each other in sequence and specificity. rpL7 fragments rich in basic amino acids could be identified as epitopes recognized by the TCR of three cell lines. Recognition of rpL7 is HLA-DR6 restricted or respectively HLA-DP restricted in the two cell lines analyzed.

[Child and adolescent psychiatry aspects of animal abuse (a comparison with aggressive patients in child and adolescent psychiatry)]. / Kinder- und jugendpsychiatrisch auffällige Tierquäler. (Ein Vergleich mit aggressiven Patienten der Kinder- und Jugendpsychiatrie).

Among 1502 aggressive children and adolescents who had been presented and treated at the Department of Child and Adolescent Psychiatry at the University of Tübingen there were 25 who had been cruel to animals. These were exclusively boys (23 out of 25). The age distribution of the zoosadists showed an increased incidence in 13, 17 and 18 year olds which is connected with problems of puberty, group constraints and proving virility. Compared with a control group of "only aggressive" patients, organic brain damage owing to complications of pregnancy or delivery, overtaxing upbringing by the parents and absence of a positive father figure could be demonstrated in the zoosadists. The hypothesis that aggressive children and adolescents have less chance to live out their aggressions in interpersonal relations use zoosadism as "evasion aggression" could only be confirmed in part. One third of the zoosadists showed additional disorders of sexual behaviour and the sexual-sadistic component was manifested in the zoosadistic action.