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PubMed1992

Characterization of immobilized anti-CD3 antibody-activated T lymphocytes for use in adoptive immunotherapy of patients with brain tumors.

Large numbers of T lymphocytes were successfully cultured for use in adoptive immunotherapy using immobilized anti-CD3 antibody. This method allows more than 1.5 x 10(10) T lymphocytes to be cultured within 2 weeks from only 20 ml of blood. Proliferated T lymphocytes were less cytotoxic than lymphokine-activated killer cells induced with a high dose of interleukin-2, but were more specific for autologous tumor cells as determined by cold target competition. Signal transduction of anti-CD3 antibody induced a population of CD8 positive cells, i.e. cytotoxic T lymphocytes. Adoptive immunotherapy using autologous lymphocytes requires a sufficient number of lymphocytes and high induced cytotoxic activity. This method is promising for clinical adoptive immunotherapy of patients with brain tumors.

Adult↗
PubMed1984

Development of hand preference in the Colorado Adoption Project.

A longitudinal study of the development of hand preference in 152 adopted and 120 nonadopted (control) infants measured in natural behavioral situations at both 12 and 24 mo. of age is reported. Significant developmental trends were observed for both increasing strength and direction of handedness. Less than 10% of the infants exhibited a clear preference at 12 mo. of age, whereas about 30% were lateralized at 24 mo., with more boys than girls being left-handed. In contrast, over 90% of the parents of these children (both biological and adoptive parents of the adopted children and parents of the nonadopted children) were lateralized. Perhaps because so few infants were lateralized at either age, parent-offspring resemblances were inconsistent and the number of significant parent/child correlations was about that expected on the basis of chance alone.

Adoption↗
PubMed1986

Epidemiological aspects of the transmission of hepatitis B by HBsAg-positive adopted children.

96 HBsAg-positive, adopted, foreign children were followed up in an epidemiological survey aimed at evaluating the risk of spreading hepatitis B in family settings. Each year 1 400-1 900 foreign children are adopted by Swedish families, 65% of them from countries in South East Asia with a high prevalence of HBsAg-positive carriers. 92% of the HBsAg-positive children came from South East Asia and 2% from Latin America. 36/96 adopted children (37.5%) transmitted hepatitis B to 54 family members. There was a considerably greater risk of transmission by younger children. 33 children less than 3 years gave rise to hepatitis in 50 family members. The greatest risk of transmitting acute hepatitis B was during the first year after the arrival of the child when 22/33 cases of acute hepatitis B (67%) occurred. 65/70 children tested for HBeAg (93%) were positive. Five had anti-e antibodies and 5 converted to anti-e during follow-up.

Adoption↗
PubMed1990

Persistent excretion of Salmonella in foreign-born adopted and native Swedish children.

The duration of salmonella excretion in 162 foreign-born adopted children and 132 native Swedish children was studied. Of the adopted children (96% being less than 1 year of age) 54% still excreted salmonella at 12 weeks, 32% at 6 months, and 12% at 1 year after arrival in Sweden. The carrier state was more prolonged in the age group 0-3 months compared to the age group greater than 6 months. In the group of native Swedish children, aged 0-5 years, 18% still excreted salmonella at 12 weeks, 4% at 6 months, and none at 1 year after the gastroenteritis episode. A majority of these children were older than 1 year. Intrafamilial transmission of salmonella seemed to be uncommon. Only 6% of the adopted children infected another family member.

Adoption↗
PubMedDate not supplied

Parents who utilize private infant adoption: an ethnographic analysis.

The purpose of this study was to gain insight into the feelings and perceptions of parents undergoing the process of private infant adoption in Western society. Ten individuals were interviewed and, through ethnographic analysis, categories and themes were derived. Participants moved sequentially through seven phases, from the choice to adopt to receiving the legal birth certificate. Adoptive parents described the phases as laden with fears and anxieties. The participants considered themselves to be risk-takers. Major themes that emerged from this study were uncertainty, unpreparedness, and commitment to an unguaranteed investment. Additional themes were isolation, competition, judgment, and ostracism from a variety of sources. Health professionals can support these parents by assisting them in establishing coping strategies and through educating them during each phase of the process.

Adaptation, Psychological↗
PubMed1999

Inhibition of lung metastasis by adoptive immunotherapy using Iscador.

Adoptive immunotherapy using spleen cells activated with Iscador was found to inhibit tumour growth significantly (P<0.001). Metastatic B16F10 tumour bearing animals treated with a single dose of spleen cells activated with Iscador (in vitro) showed 100% inhibition of tumour nodule formation on 21st day. Single injection of splenocytes isolated from mice treated with Iscador inhibited the tumour nodule formation by 93.8%. Animals treated with in vivo and in vitro activated spleen cells along with Iscador had an increase in life span of 119% and 81% respectively. Treatment of animals with low dose of Iscador after adoptive immunotherapy further augmented the life span. Animals which underwent adoptive immunotherapy showed significantly reduced lung collagen hydroxyproline (9.8 microg/mg protein) and serum sialic acid (24.61 micro/ml serum) levels compared to control tumour bearing animals with increased levels of lung hydroxyproline (26.95 microg/mg protein) and serum sialic acid levels (151.3 microg/ml serum). Serum gamma -glutamyl transpeptidase levels were found to be significantly reduced in the group of animals treated with Iscador and Iscador activated splenocytes (16.6+/-2.3 nmol P-nitroaniline released /ml serum) Group of animals treated with Iscador activated splenocytes alone also showed significantly reduced serum gamma - glutamyl transpeptidase levels (17.3+/-10 nmol P-nitroaniline released /ml serum) compared to control tumour bearing animals (91+/-12 nmol P-nitroaniline released /ml serum).

Animals↗
PubMed2000

Adoptive transfer murine model of granulomatous experimental autoimmune thyroiditis.

Experimental autoimmune thyroiditis (EAT) is a chronic inflammatory autoimmune disease that can be induced in genetically susceptible animals by immunization with mouse thyroglobulin (MTg) in an appropriate adjuvant or by the adoptive transfer of MTg-sensitized donor spleen cells, activated in vitro with MTg, into naive recipients. In the adoptive transfer model used in our laboratory, donor cells activated with MTg alone induce a relatively mild chronic lymphocytic form of EAT (L-EAT), in which the thyroid infiltrate consists primarily of mononuclear cells, and the thyroid inflammation persists for several months. When the same donor cells are activated with MTg together with anti-IL-2R and/or IL-12, a more severe and histologically distinct granulomatous form of EAT is induced in recipient mice. In addition to having distinct histopathologic features, granulomatous EAT (G-EAT) differs from L-EAT in that granulomatous thyroid lesions are not chronic. After reaching maximal severity 21 days after cell transfer, G-EAT thyroid lesions either resolve or the thyroids become atrophic and fibrotic by day 35. In this review, the histopathologic features of G-EAT and L-EAT are described, and our studies with the adoptive transfer G-EAT model which have focused on the mechanisms involved in induction of G-EAT in mice, and the evolution of G-EAT lesions to resolution of inflammation or fibrosis, are reviewed.

Adoptive Transfer↗
PubMed2000

IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is induced in the SJL/J mouse by adoptive transfer of activated proteolipid protein peptide (PLP) 139-151-specific Th1 cells. T cells responding to altered peptide ligands (APL) of PLP, previously shown to induce Th2 differentiation and regulate disease in PLP-immunized mice, do not transfer EAE. However, the exact mechanism of disease regulation by APL-specific T cells has not been elucidated. In this report, we show that 1F1, a Th2 clone specific for an APL of PLP139-151 can prevent adoptive transfer of EAE when cocultured with PLP-encephalitogenic spleen cells (PLP-spleen). Cytokines from activated 1F1 cells were detected by hybridization of mRNA to oligonucleotide arrays (DNA chip) and by ELISA. The Th2 cytokines found to be present at the highest protein and mRNA levels were evaluated for their role in suppression of adoptive transfer of EAE from PLP-activated spleen cell cultures. Abs to individual cytokines in 1F1 PLP-spleen cocultures suggested that IL-4, IL-13, and TGF-beta played a significant role in suppressing EAE. Abs to the combination of IL-4, IL-10, IL-13, and TGF-beta completely neutralized the protective effect of 1F1. Addition of Th2 cytokines to PLP-spleen cultures showed that IL-13 and TGF-beta were each individually effective and low levels of IL-4 synergized with IL-13 to inhibit disease transfer. IL-5, IL-9, and IL-10 had little or no effect whereas GM-CSF slightly enhanced EAE. Our results demonstrate that Th2 cytokines derived from APL-specific Th2 cells can effectively down-regulate the encephalitogenic potential of PLP-spleen cells if present during their reactivation in culture.

Adoptive Transfer↗
PubMed2001

The role of adoptively transferred CD8 T cells and host cells in the control of the growth of the EG7 thymoma: factors that determine the relative effectiveness and homing properties of Tc1 and Tc2 effectors.

We had previously examined the factors that regulate the response of OVA-specific TCR-transgenic CD8 T cells to the B16 OVA melanoma, growing as lung metastases. We examine here whether the same parameters operate for EG7, growing intradermally. Tc1 or Tc2 CD8 effector cells from OT-1 mice were injected either mixed with the tumor or i.v. at day 0 or 7. Tc2 were one-fifth to one-tenth as effective as Tc1 when injected with the tumor, in controlling tumor growth, but were only 1/20 to 1/100 injected i.v. Tc1 injected i.v. entered the draining lymph nodes faster than Tc2 and caused a faster accumulation of host cells. Both caused an abrupt termination of host cell entry into lymph nodes and spleen after tumor elimination, but this occurred earlier for Tc1 than for Tc2. Host responses were ineffective in the absence of adoptive transfer but were essential after transfer. Perforin expression in the donor cells plays no role in adoptively transferred Tc1 or Tc2 control of the tumor, and neither IL-4 nor IL5 is needed for Tc1 or Tc2 function. Tc1 cells from mice lacking IFN-gamma, however, control tumor growth less well, whereas Tc2 effectors lacking IFN-gamma are unaffected. Tc1 from IFN-gamma-deficient mice attract fewer host cells to the draining lymph node, whereas Tc1 cells from perforin-deficient donors are unimpaired. We conclude that host cell recruitment is a crucial element in adoptive immunotherapy. The differences between the EG7 and the previous B16 melanoma model are discussed.

Adoptive Transfer↗
PubMed2001

Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor.

Therapeutic efficacy of adoptive immunotherapy of malignancies is proportional to the number of effector T cells transferred. Traditionally, exogenous IL-2 treatment has been used to promote the survival and function of transferred cells. Recently, we described the therapeutic effects of in vivo ligation of the costimulatory receptor, OX-40R, on activated T cells during early tumor growth. In this study, we examined the effects of IL-2 and OX-40R mAb on adoptive immunotherapy of advanced tumors. For treatment of 10-day 3-methylcholanthrene 205 pulmonary metastases, systemic transfer of 50 x 10(6) activated tumor-draining lymph node T cells resulted in >99% reduction of metastatic nodules. With either IL-2 or OX-40R mAb conjunctional treatment, only 20 x 10(6) cells were required. Advanced 10-day 3-methylcholanthrene 205 intracranial tumors could be cured by the transfer of 15 x 10(6) L-selectin(low) T cells derived from draining lymph nodes. In this situation, IL-2 administration inhibited therapeutic effects of the transferred cells. By contrast, 5 x 10(6) T cells were sufficient to cure all mice if OX-40R mAb was administrated. Studies on trafficking of systemically transferred T cells revealed that IL-2, but not OX-40R mAb, impeded tumor infiltration by T cells. Tumor regression required participation of both CD4 and CD8 T cells. Because only CD4 T cells expressed OX-40R at cell transfer, direct CD4 T cell activation is possible. Alternatively, OX-40R might be up-regulated on transferred T cells at the tumor site, rendering them reactive to the mAb. Our study suggests OX-40R mAb to be a reagent of choice to augment T cell adoptive immunotherapy in clinical trials.

Adjuvants, Immunologic↗
PubMed2003

The Fas/Fas ligand pathway is important for optimal tumor regression in a mouse model of CTL adoptive immunotherapy of experimental CMS4 lung metastases.

The mechanisms of CTL-mediated tumor regression in vivo remain to be fully understood. If CTL do mediate tumor regression in vivo by direct cytotoxicity, this may occur via two major effector mechanisms involving the secretion of perforin/granzymes and/or engagement of Fas by Fas ligand (FasL) expressed by the activated CTL. Although the perforin pathway has been considered the dominant player, it is unclear whether Fas-mediated cytotoxicity is additionally required for optimal tumor rejection. Previously, we produced H-2L(d)-restricted CTL reactive against the CMS4 sarcoma, which expresses a naturally occurring rejection Ag recognized by these CTL and harbors a cytokine (IFN-gamma plus TNF)-inducible, Fas-responsive phenotype. The adoptive transfer of these CTL to syngeneic BALB/c mice with minimal (day 3 established) or extensive (day 10 established) experimental pulmonary metastases resulted in strong antitumor responses. Here we investigated whether a FasL-dependent CTL effector mechanism was important for optimal tumor regression in this adoptive immunotherapy model. The approach taken was to compare the therapeutic efficacy of wild-type to FasL-deficient (gld) CTL clones by adoptive transfer. In comparison with wild-type CTL, gld-CTL efficiently mediated tumor cytolysis and produced comparable amounts of IFN-gamma, after tumor-specific stimulation, as in vitro assessments of Ag recognition. Moreover, gld-CTL mediated comparably potent antitumor effects in a minimal disease setting, but were significantly less effective under conditions of an extensive tumor burden. Overall, under conditions of extensive lung metastases, these data revealed for the first time an important role for a FasL-dependent CTL effector mechanism in optimal tumor regression.

Animals↗
PubMed2006

CTL adoptive immunotherapy concurrently mediates tumor regression and tumor escape.

Tumor escape and recurrence are major impediments for successful immunotherapy. It is well-documented that the emergence of Ag-loss variants, as well as regulatory mechanisms suppressing T cell function, have been linked to inadequate antitumor activity. However, little is known regarding the role of Fas-mediated cytotoxicity by tumor-specific CD8(+) CTL in causing immune evasion of Fas resistant variants during adoptive immunotherapy. In this study, we made use of an adoptive transfer model of experimental lung metastasis using tumor-specific CTL as a relevant immune-based selective pressure, and wherein the Fas ligand pathway was involved in the antitumor response. Surviving tumor cells were recovered and examined for alterations in antigenic, functional, and biologic properties. We showed that diminished susceptibility to Fas-mediated cytotoxicity in vivo was an important determinant of tumor escape following CTL-based immunotherapy. Tumor escape variants (TEV) recovered from the lungs of CTL-treated mice exhibited more aggressive behavior in vivo. However, these TEV retained relevant MHC class I and tumor Ag expression and sensitivity to CTL via the perforin pathway but reduced susceptibility to Fas-mediated lysis. Moreover, TEV were significantly less responsive to eradication by CTL adoptive immunotherapy paradigms as a consequence of increased Fas resistance. Overall, we identified that Fas(low)-TEV emerged as a direct consequence of CTL-tumor interactions in vivo, and that such an altered neoplastic Fas phenotype compromised immunotherapy efficacy. Together, these findings may have important implications for both tumor progression and the design of immunotherapeutic interventions to confront these selective pressures or escape mechanisms.

Animals↗
PubMed1976

The influence of some parental characteristics on children's primary abilities and field independence: a study of adopted children.

The Children's Embedded Figures Test and measures of V, P, N and S abilities were administered to 5-7-year-old Belgian children (33 boys and 36 girls) adopted early in life. These child variables were correlated with the main factorial dimensions of the adoptive parents' answers on the Parental Attitude Research Instrument and on Buehler's Life Goals Inventory and with the adoptive mother's child-rearing practices, determined through an interview. The PARI dimensions were unrelated to children's test performances. Reinforcement of competition and independence, an interview variable, was significantly related to several ability measures and to the CEFT, especially in girls. The significant correlations of some LGI dimensions with boys' and/or girls' primary abilities were interpreted by referring to the influence on the development of children's abilities of a future-oriented attitude toward learning and memory and of a warm parent-child interaction.

Adoption↗
PubMed1982

Medicaid program; entitlement of children for whom payments are made under the foster care maintenance payments program or the adoption assistance program--HCFA. Final rule.

These final regulations implement the Medicaid provisions of the Adoption Assistance and Child Welfare Act of 1980 (Pub. L. 96-272). That law established a new title IV-E of the Social Security Act, providing for adoption subsidies for certain hard-to-place children and for an expanded foster care program. Under the law, children for whom adoption assistance of foster care maintenance payments are made are entitled to Medicaid. These final regulations specify that the State making payments for a child under its title IV-E program is also responsible for Medicaid for that child.

Adoption↗
PubMedDate not supplied

Adopting children with attachment problems.

This article describes children with significant attachment problems and summarizes the actions needed to increase the probability that such children can be successfully adopted. Healthy and disordered attachment patterns are detailed, as well as the principles and strategies that are important in parenting such children and the parenting characteristics that should be sought in selecting families for children with attachment disorder. Psychological treatment and other postadoption services necessary to support the adoption and the child's ability to successfully form a secure attachment with the adoptive parents are also highlighted.

Adoption↗
PubMed2000

Adoptive cellular therapy.

We provide a current review of adoptive cellular therapy in the management of metastatic renal cell carcinoma. A comprehensive literature review of peer-reviewed articles on the development and use of adoptive cellular immunotherapy was performed. Renal cell carcinoma is a highly immunogenic tumor that has proven resistant to standard cytotoxic chemotherapy, but has shown reproducible response to immune-based therapy. In an effort to improve responses, a variety of adoptive cellular strategies have been devised and tested in the setting of metastatic disease. Among the techniques developed, the use of lymphokine-activated killer (LAK) cells, autolymphocyte therapy (ALT), and tumor-infiltrating lymphocytes (TIL) have been the best studied. While further trials are ongoing, thus far, these approaches have not consistently shown benefit in comparison to standard immune-based treatment with biologic response modifiers, most importantly, high-dose bolus interleukin-2 (IL-2). Future approaches, including the use of dendritic cells (DC) to facilitate the development of tumor vaccines, are encouraging. Advanced renal cell carcinoma continues to inspire research of promising new cellular immunotherapeutics. The experience with LAK, ALT, and TIL has greatly increased our understanding of tumor immunobiology, and has led to the ongoing development of new technology, including DC, vaccine, and antibody therapy.

Adjuvants, Immunologic↗
PubMed2000

Generation and purification of CD8+ melan-A-specific cytotoxic T lymphocytes for adoptive transfer in tumor immunotherapy.

Tumor antigens that might serve as potential targets for adoptive T-cell therapy have been defined in different tumor entities, especially in malignant melanoma. To generate conditions to induce primary T-cell responses against different HLA-A*0201-restricted melanoma peptides and to allow further expansion of peptide-specific T cells for adoptive transfer, CD8+-purified T cells from healthy donors were stimulated with Melan-A-pulsed autologous dendritic cells. Dendritic cells were generated in vitro from monocytes with granulocyte macrophage colony-stimulating factor, interleukin-4, and transforming growth factor-beta1. After 3-4 weekly stimulation cycles with Melan-A-pulsed DCs, we were able to induce a strong peptide-specific CTL response in vitro. MHC-peptide tetramer staining revealed a frequency of up to 3.5% CD8+/Melan-A+ T cells. Additional antigen-independent expansion with anti-CD3/anti-CD28 monoclonal antibodies together with interleukin-2 gave rise to 600-fold expansion of CD8+ CTLs that maintained Melan-A specificity and were able to efficiently lyse Melan-A-expressing melanoma cells. To enrich antigen-specific T cells in vitro, we used a recently established technology for analysis and sorting of live cells according to secreted cytokines. In the present study, we demonstrated that Melan-A-specific T cells can be purified by magnetic separation according to secreted IFN-gamma. These cells revealed a very potent monospecific CTL response, even at low E:T ratios, against Melan-A-pulsed and Melan-A-expressing target cells. Altogether, our study demonstrated that we have developed an efficient method for generating large numbers of peptide-specific T cells in vitro that may be used for adoptive T-cell transfer in tumor immunotherapy.

Adoptive Transfer↗
PubMed2000

[Transnational adoptions. Medical and ethical issues].

OBJECTIVE: To report our experience in the problems of international adoptions and their characteristics and management. MATERIALS AND METHODS: Review of patients treated in our pediatrics department and review of the literature. COMMENT: The adoption of children from other countries is increasing in Spain. The problems presented by these children include infectious diseases, and nutritional and psycho-emotional disorders. Furthermore, pediatricians should take ethical issues into account and discuss them with the adoptive parents.

Adolescent↗