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PubMedDate not supplied

Feasibility study of adoptive immunotherapy for metastatic lung tumors using peptide-pulsed dendritic cell-activated killer (PDAK) cells.

We have established a novel culture system to generate effector lymphocytes designated as peptide-pulsed dendritic cell-activated killer (PDAK) cells using cultured dendritic cells (DCs), synthetic peptide, peripheral blood lymphocytes, and interleukin-2 plus immobilized anti-CD3 antibody. A feasibility study of an adoptive immunotherapy trial using PDAK cells was conducted on HLA-A2 and HLA-A24 cancer patients with antigen-positive lung metastasis that was defined by serological analysis or PCR analysis. Eleven patients with lung metastasis participated in the study: 6 with colorectal cancer, 2 with pancreatic cancer, 1 each with breast and lung cancer, and 1 with melanoma. The patients received either Muc-1, CEA, gpl00, Her-2 or SART-3-PDAK cells generated in vitro, intravenously in combination with 350,000 U IL-2 weekly for 9 weeks, together with a planned dose-escalation schedule of three transfers each of 1 x 10(7), 3 x 10(7) and 1 x 10(8) PDAK cells/kg for 6 patients, and with a uniform dose of 3 x 10(7) PDAK cells/kg for the remaining 5 patients. Peptide/HLA-specific cytotoxic activity and TCRVbeta gene usage of PDAK cells were analyzed. All transfers of PDAK cells, which showed peptide/HLA-specific lysis, were well-tolerated in all patients, and adverse effects (elevation of transaminase, fever, and headache) were observed primarily at grade 1, but in no case greater than grade 2. The generation of sufficient cells to treat the patients with 3 x 10(7) PDAK cells/kg was feasible using our culture system, but we were able to generate and administer the dose of 1 x 10(8) PDAK cells/kg in only one patient. One partial response (PR) of lung metastasis occurred in a pancreatic cancer patient who received 3 x 10(7) Muc-1-PDAK cells/kg. The cytolytic units of PDAK cells in this patient appeared to be substantially higher compared to those in PD patients. TCR gene usage analysis on PDAK cells revealed preferential usage of TCRVbeta segments. These results suggest that adoptive immunotherapy using PDAK cells for cancer patients with antigen-positive lung metastasis is safe and feasible, and tumor response should be examined in a future clinical trial

Adult↗
PubMedDate not supplied

Permanency mediation: a path to open adoption for children in out-of-home care.

This research study examined the experiences of birthparents, permanent parents, and mediators in permanency mediation following a state child welfare agency's recommendation for termination of parental rights. Permanency mediation provides participants with the opportunity to collaborate in an agreement that entails a voluntary surrender of parental rights by the birthparents and the placement of children with permanent parents in open adoption or guardianship. Findings suggested that permanency mediation has the potential to be a successful practice. Participants, however, need additional support during and after mediation to help them understand open adoption and deal with the changes in family structures and boundaries, address their own feelings and concerns, and establish reliable means of communication with each other.

Adoption↗
PubMed2004

From chaos to developmental growth: Working through trauma to achieve adolescence in the analysis of an adopted Russian orphan.

In seven years of treatment beginning with an extended evaluation/psychotherapy phase of one year's duration followed by a six-year analysis, a picture emerged shedding light on the resilience of this child who had at first appeared too disturbed and intellectually limited to benefit from an analysis. Her first seventeen months of life were spent with her mother in the otherwise deplorable physical conditions of a Russian prison cell. From there she went to at least two different orphanages before being adopted by American parents when she was seven and a half. With analytic treatment, Nikita evolved from a traumatized child, whose inner world reflected the many losses and abuses she had suffered, to a competent adolescent equipped to use the loving relationships her adoptive parents offered her. Analysis of defense, labeling of affects, and use of the analyst as a developmental object all contributed to the therapeutic action and to my patient's modification of sadomasochistic and narcissistic defenses allowing her to fully develop her capacity for mentalization.

Adolescent↗
PubMed2006

Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells.

A 29-year-old female breast cancer patient with multiple bone metastases (HLA-A2) was treated with adoptive transfer using autologous peripheral blood mononuclear cells (PBMCs) activated with the HLA-A2-matched allogeneic GC022588 gastric cancer cell line and interleukin-2 plus an immobilized anti-CD3 antibody culture system. The relief of bone pain in parallel with a decrease of serum carcinoembryonic antigen levels was obtained just after the administration of GC022588-activated effector lymphocytes, and a good quality of life was accomplished for 4 months. The GC022588-activated effector lymphocytes included 44% CD4+, 77% CD8+, and 26% CD4+CD8+ phenotypes, and expressed 25% killing activity against GC022588 stimulator cells at an E/T ratio of 50:1. T cell receptor (TCR) usage analysis for the effector cells showed oligoclonal expression of TCRVbeta1, 3, 9, and 11, especially TCRVbeta5.2, 12, 13.1 and 17, and their killing activity was significantly inhibited in the presence of anti-TCRalphabeta antibody and anti-TCRVbeta12 antibody. SSCP analysis revealed clonotypic bands of TCRVbeta12. These results suggest that shared antigens exist between breast and gastric adenocarcinomas. Allogeneic tumor cells can stimulate PBMCs to generate effector cells with selected TCRCDR3 usages that recognize tumor antigens. These effector lymphocytes may be good candidates for the adoptive immunotherapy of cancer.

CD3 Complex↗
PubMed2006

[Anaemia in adopted children, not always iron deficiency].

Anaemia was diagnosed in four adopted children during a standard screening examination 1-4 weeks after arrival. Further investigation revealed a number of causes which could then be specifically treated. The children were a girl aged 14 months from China with iron-deficiency anaemia, a boy aged 16 months from Nigeria with sickle cell anaemia, a girl aged 5 from Haiti who had alpha-thalassaemia, and a boy aged 7 from Brazil with spherocytosis. Iron deficiency is the most common cause of anaemia in childhood. However, in adopted children from sub-tropical areas other causes of anaemia like haemoglobinopathies or erythrocyte membrane defects should be borne in mind, particularly as a history of disease and family history are often lacking. Additional investigations may be necessary. An incorrect diagnosis of iron deficiency may result in ongoing and unjustified iron supplementation leading to harmful iron accumulation in thalassaemia and a delay in the correct treatment in sickle cell anemia or spherocytosis which could carry considerable risk.

Adoption↗
PubMed1990

Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy.

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.

Adult↗
PubMed1990

[Study on the mechanism of tumor regression by adoptive immunochemotherapy in mice].

The mechanism of tumor regression by adoptive immunochemotherapy has been unknown. We examined tumor infiltrating lymphocytes (TILs) and cytokines, using immunohistochemical staining and the histo in situ hybridization (HISH) technique, on Meth A tumor in regression of BALB/c mice. In addition, we examined cytokine activity in the serum of mice with a tumor in regression. The result of immunohistochemical staining showed that the number of Thy-1+ cells, Lyt-1+ cells, OKIa1+ cells all increased in the tumors in regression compared to those in the tumors in non-regression. However, there were no these TILs in the necrotic part of tumor. This result suggested that TILs released substances which might include cytokines. A small number of each cytokine mRNA was observed, using HISH with cytokine DNA probes. TNF-alpha, and -beta mRNA were observed in both he tumors in regression and non-regression; while, IFN-beta and -gamma mRNA were observed only in the tumor in regression. TNF-alpha activity in the serum of tumor in regression group was higher than that of he tumor in non-regression group. IFN activity in the serum of the tumor in regression group started increasing after adoptive immunochemotherapy. These results show that cytokines as well as TILs have important roles in tumor regression.

Animals↗
PubMedDate not supplied

A case of recurrent ovarian cancer successfully treated with adoptive immunotherapy and lentinan.

BACKGROUND: Immunotherapy is useful for the prevention of the post-operative recurrence of some types of cancer and, in combination with certain anticancer drugs, is expected to prolong survival time. However, the clinical efficacy of immunotherapy alone against advanced cancer has not yet been demonstrated. CASE REPORT: A 67-year-old woman with ovarian cancer who had undergone post-operative adjuvant chemotherapy suffered from recurrent cancer in the lymph nodes. A partial response to adoptive immunotherapy and the administration of the biological response modifier, lentinan containing beta-glucan as the principal component, was maintained for five months without the use of chemotherapy. CONCLUSION: Adoptive immunotherapy with lentinan alone was potentially useful for the treatment of lymph node metastases from ovarian cancer.

Aged↗
PubMed1991

Local adoptive immunotherapy using lymphokine-activated killer cells and interleukin-2 against malignant pleural mesothelioma: report of two cases.

Malignant pleural mesothelioma is refractory to conventional therapy. We tried local adoptive immunotherapy using lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) to control malignant pleural effusion due to mesothelioma in two patients: Case 1 was that of a 69-year-old man, and Case 2 that of a 49-year-old woman with complicating chronic idiopathic thrombocytopenic purpura. A systemic survey revealed no sign of metastasis in either case. Intrapleural instillations of 6.7 x 10(9) autologous LAK cells in Case 1, or 11.3 x 10(9) allogeneic LAK cells in Case 2, with daily injections of IL-2 resulted in reductions of the pleural effusions in each case and in a decline in the level of hyaluronic acid in the effusion, in Case 1. The instillations of autologous and allogeneic LAK cells were well tolerated. The results suggest that local adoptive immunotherapy could be useful in the treatment of malignant effusion due to mesothelioma.

Aged↗
PubMed1991

What about adopters?

Alison Stewart and Wendy Ring consider the adjustments people who adopt have to make when becoming parents. They outline a scheme to offer parentcraft to adopters and consider the implications for health visiting of this minority group.

Adaptation, Psychological↗
PubMedDate not supplied

Adoption outcomes for children with handicaps.

About 800 families who had adopted children with special needs responded to a mailed survey. Most reported good adoption outcomes. The presence of a handicap--vision, hearing, or physical impairment, mental retardation, or serious medical condition--was not an important factor influencing outcome.

Adolescent↗
PubMed1991

[Adoptive immunotherapy for pulmonary tuberculosis caused by multi-resistant bacteria using autologous peripheral blood leucocytes sensitized with killed Mycobacterium tuberculosis bacteria].

A patient with pulmonary tuberculosis caused by bacteria resistant to various anti-microbial agents was treated with adoptively transferred autologous peripheral blood leucocytes (PBL) sensitized with killed Mycobacterium tuberculosis organisms in vitro. The 32-year-old man was admitted to our hospital from National Sanitarium Okinawa Hospital with weight loss, high fever, and rapid aggravation on chest X-ray. Patient's PBL obtained by leukapheresis and separated with Ficoll-Hypaque solution were cultured with killed Mycobacterium tuberculosis bacteria of 0.4 microgram per ml at 1 x 10(6) cells per ml for 7 days in media containing 0.5 U recombinant 1L-2 per ml. After incubation, PBL were layered and centrifuged on Ficoll-Hypaque solution and washed three times with saline. PBL (1-3 x 10(8)) were combined and concentrated for infusion in 20 to 30 ml saline. After injection, patient displayed fever and transitory drop of PaO2. Although the patient did not have an improved on chest X-ray, his fever was alleviated, weight was increased, accelerated ESR was slightly improved, and the number of organisms in sputum (Number of Gaffky) temporarily decreased. Adoptive immunotherapy using the autologous PBL which were sensitized with killed bacteria may be an effective anti-tuberculous immunotherapy.

Adult↗
PubMed1990

[Some reflexions to guide the parents toward adoption].

The successive steps of the long way facing all French couples applying for child adoption are described. Main problems are the legal adoption authorization, the origin of children (French children under the care of the State, foreign children either through private institutions or after an individual approach). Pediatricians play an important role in counselling and evaluating the health status of the children (study of medical files, requests for biochemical tests) before the formal decision is made.

Adoption↗
PubMed1990

Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model.

A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC). The antitumor effect of IL-2 alone was not present in the irradiated mice. A highly significant difference persisted between group IIA and all other groups. There was no difference in the histologic characteristics of tumors in control mice and in mice with inhibited tumor growth treated with IL-2 or IL-2 and human LAK cells. These results show that adoptive immunotherapy with human LAK cells and human recombinant IL-2 is effective against human pancreatic cancer growing in nude mice. This effect is independent from antitumor activity from IL-2 administrations alone.

Animals↗
PubMed1989

An experimental approach to specific adoptive immunotherapy for malignant brain tumors.

With the aid of interleukin 2 (IL-2), two phenotypically different cytotoxic T lymphocyte (CTL) clones were established with target specificity against syngeneic murine malignant brain tumor (a methylcholanthrene-induce ependymoblastoma of C57BL/6 mouse origin, 203-glioma). Furthermore, the cloned CTL lines were characterized in vitro, and their in vivo effectiveness was investigated by intracerebral (i.c.) tumor neutralization assay and adoptive immunotherapy with the clones for i.c. tumor-bearing mice. Each CTL clone retained an IL-2 dependency with a defined functional activity. G-CTLL 1 with a phenotype of Lyt-1-.2.3+ exhibited a target cytotoxicity against 2 kinds of murine glioma cells, syngeneic 203-glioma and allogeneic RSV-M glioma (Schmitt-Ruppin rous sarcoma virus-induced malignant astrocytoma). It is noted that G-CTLL 1 cells produced gamma interferon (IFN) by stimulation with glioma antigens. The spontaneous release of gamma IFN paralleled the amounts of exogenous IL-2 added into the cultures, but IL-2 had no synergistic effects on IFN release in the presence of tumor antigens. Furthermore, by adding anti-mouse gamma IFN antibody, the IFN production of G-CTLL 1 cells was inhibited but their lytic potential was hardly reduced in vitro. In contrast, G-CTLL 2 cells expressed a cell surface phenotype of Lyt-1+.2.3+ with more restricted target specificity against only syngeneic 203-glioma cells, although they showed a weaker cytotoxicity than G-CTLL 1 cells and no release of gamma IFN. The in vivo therapeutic efficacy using G-CTLL 1 cells was confirmed in both adoptive immunotherapy and tumor neutralization assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Genetic and environmental influences on obesity assessed by the adoption method.

Obesity is usually defined on the basis of deviations in cross-sectional population distribution of body mass. However, it is a heterogenous condition in terms of the changes of the individual body mass over time--there is a, probably life-long, tracking tendency, but also a considerable super-imposed age-dependent as well as age-independent variation over time. The tracking level as well as the fluctuation may be influenced by genes, environment, and gene-environment interactions. The longitudinal studies of subjects adopted-away early in life and their biological and adoptive relatives may be a particularly powerful method for assessment of the effects of genes and environment on obesity considered as a continuous trait both in terms of body mass and time.

Adoption↗
PubMed1989

[Consent to adoption].

Many legal provisions exist that aim at preventing children from being abandoned. However, in some instances, these apparently beneficial measures result in de facto abandonments. In such cases, the abandonment is delayed, and as a result the child is no longer eligible for adoption. This situation leads to a number of successive changes that are emotionally detrimental to the child. We need prophylactic measures aimed at obtaining the "consent to adoption" from mothers who obviously feel and are incapable of being mothers in the full sense of the term.

Abortion, Induced↗