Development of a T Cell Receptor Targeting an HLA-A*0201 Restricted Epitope from the Cancer-Testis Antigen SSX2 for Adoptive Immunotherapy of Cancer.

The clinical success of adoptive immunotherapy of cancer relies on the selection of target antigens that are highly expressed in tumor cells but absent in essential normal tissues. A group of genes that encode the cancer/testis or cancer germline antigens have been proposed as ideal targets for immunotherapy due to their high expression in multiple cancer types and their restricted expression in immunoprivileged normal tissues. In the present work we report the isolation and characterization of human T cell receptors (TCRs) with specificity for synovial sarcoma X breakpoint 2 (SSX2), a cancer/testis antigen expressed in melanoma, prostate cancer, lymphoma, multiple myeloma and pancreatic cancer, among other tumors. We isolated seven HLA-A2 restricted T cell receptors from natural T cell clones derived from tumor-infiltrated lymph nodes of two SSX2-seropositive melanoma patients, and selected four TCRs for cloning into retroviral vectors. Peripheral blood lymphocytes (PBL) transduced with three of four SSX2 TCRs showed SSX241-49 (KASEKIFYV) peptide specific reactivity, tumor cell recognition and tetramer binding. One of these, TCR-5, exhibited tetramer binding in both CD4 and CD8 cells and was selected for further studies. Antigen-specific and HLA-A*0201-restricted interferon-γ release, cell lysis and lymphocyte proliferation was observed following culture of TCR engineered human PBL with relevant tumor cell lines. Codon optimization was found to increase TCR-5 expression in transduced T cells, and this construct has been selected for development of clinical grade viral vector producing cells. The tumor-specific pattern of expression of SSX2, along with the potent and selective activity of TCR-5, makes this TCR an attractive candidate for potential TCR gene therapy to treat multiple cancer histologies.

Kinship in entrepreneur networks: Performance effects of resource assembly in Africa

We examine the relationship between structural social capital, resource assembly, and firm performance of entrepreneurs in Africa. We posit that social capital primarily composed of kinship or family ties helps the entrepreneur to raise resources, but it does so at a cost. Using data drawn from small firms in Kampala, Uganda, we explore how shared identity among the entrepreneur's social network moderates this relationship. A large network contributed a higher quantity of resources raised, but at a higher cost when shared identity was high. We discuss the implications of these findings for the role of family ties and social capital in resource assembly, with an emphasis on developing economies.

In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies.

Hit parade for adoptive cell transfer therapy: the best T cells for superior clinical responses.

Adoptive cell transfer (ACT) of T cells has great clinical potential, but the numerous variables of this therapy make choices difficult. A new study takes advantage of a novel technology for characterizing the T-cell responses of patients. If applied systematically, this approach may identify biomedical correlates of protection, thereby supporting treatment optimization.

How demography, life history, and kinship shape the evolution of genomic imprinting.

How phenomena like helping, dispersal, or the sex ratio evolve depends critically on demographic and life-history factors. One phenotype that is of particular interest to biologists is genomic imprinting, which results in parent-of-origin-specific gene expression and thus deviates from the predictions of Mendel's rules. The most prominent explanation for the evolution of genomic imprinting, the kinship theory, originally specified that multiple paternity can cause the evolution of imprinting when offspring affect maternal resource provisioning. Most models of the kinship theory do not detail how population subdivision, demography, and life history affect the evolution of imprinting. In this work, we embed the classic kinship theory within an island model of population structure and allow for diverse demographic and life-history features to affect the direction of selection on imprinting. We find that population structure does not change how multiple paternity affects the evolution of imprinting under the classic kinship theory. However, if the degree of multiple paternity is not too large, we find that sex-specific migration and survival and generation overlap are the primary factors determining which allele is silenced. This indicates that imprinting can evolve purely as a result of sex-related asymmetries in the demographic structure or life history of a species.

Kinship, ritual kinship and political milieus in an alpine Valley in 19th century

In my paper I will present some results about ritual kinship and political mobilization of popular groups in an alpine Valley: the Val de Bagnes, in the Swiss canton of Valais. There are two major reasons to choose the Val de Bagnes for our inquiry about social networks: the existence of sharp political and social conflicts during the 18th and the 19th century and the availability of almost systematic genealogical data between 1700 and 1900. The starting point of my research focuses on this question: what role did kinship and ritual kinship play in the political mobilization of popular groups and in the organization of competing factions? This question allows us to shed light on some other uses and meanings of ritual kinship in the local society. Was ritual kinship a significant instrument for economic cooperation? Or was it a channel for patronage or for privileged social contacts? The analysis highlights the importance of kinship and godparentage for the building of homogeneous social and political networks. If we consider transactions between individuals, the analysis of 19th century Val de Bagnes gives the impression of quite open networks. Men and women tried to diversify their relations in order to avoid strong dependency from powerful patrons. Nevertheless, when we consider the family networks, we can notice that most relations took place in a structured social space or a specific "milieu", were intense contacts enhanced trust, although political allegiances and social choices were not fully predictable on the basis of such preferential patterns. In a politically conflictual society, like 19th century Bagnes, ritual kinship interacted with kinship solidarities and ideological factors shaping dense social networks mostly based on a common political orientation. Such milieus sustained the building of political factions, which show surprising stability over time. In this sense, milieus are important factors to understand political and religious polarization in 19th century Switzerland.

The biological family from the perspective of kinship fostered adolescents

Background: Previous studies emphasise the importance of the biological family to the welfare of fostered adolescents. However, the majority of these studies only take into consideration the viewpoints of the professionals, foster parents and biological parents not those of the adolescents themselves. For this reason little is known about the perceptions the adolescents have and the needs they express. Method: This study has gathered data from 57 adolescents in kinship family fostering in Spain (AFE). The study applied qualitative reseach, using focus groups to gather data and the Atlas.ti programme to analyse the data. The qualitative data give us a more profound understanding of how the fostered adolescents relate to their biological families. Results: The results highlight the specific needs of these adolescents a) an understanding of their family history b) the impact of visits from and relationship with their biological family and c) the relationship between the biological family and the foster family. Conclusions: These findings reveal implications to consider when creating support programmes aimed at this group.

The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28-Costimulated T Cells Prepared for Adoptive Therapy.

PURPOSE: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy. EXPERIMENTAL DESIGN: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer. RESULTS: The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4, and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12, and CXCL16 are expressed quasi-universally, including in tumors lacking tumor-infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed Tcells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer. CONCLUSIONS: DC-primed tumor-specific T cells are armed with the appropriate receptors to migrate toward universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating toward these chemokines. Clin Cancer Res; 21(12); 2840-50. ©2015 AACR.

Kinship foster care: a study from the perspective of the of the caregivers, the children and the child welfare workers

In the last twenty years, in most Western countries, kinship foster care has become an integral part of childcare systems,growing progressively with regard to the numbers of children involved and relative weight as a care resource within thesystem; indeed, in some countries it is even more common than other placement options, such as non-kinship foster careand residential care. Research on this phenomenon is still recent and scarce, and there are few programmes targeting thispopulation. In this article we present the results of a descriptive study on kinship foster care in the city of Barcelona,including information and data from the different stakeholders involved. From a quality of life research perspective weanalyze the perceptions, evaluation and expressed satisfaction of caregivers, children and practitioners from the specialistChild and Adolescent Teams (EAIAs) responsible for the study and follow-up of kinship foster care cases. The researchpresented results are in line with those of current research in this field, and lays the basis for the future development ofkinship foster care programmes

Acogimiento en familia extensa: un estudio desde la perspectiva de los acogedores, de los niños y niñas acogidos y de los profesionales que intervienen. = Kinship foster care: a study from the perspective of the caregivers, the children and the child welfare workers

Desde hace aproximadamente dos décadas, en la mayoría de los países occidentales, los acogimientos en familia extensa han entrado a formar parte de los sistemas de protección infantil, siguiendo una evolución creciente en cuanto a número y peso especifico como recurso de acogimiento. Las investigaciones sobre este fenómeno son aún recientes y escasas como también lo son los programas dirigidos a esta población. En el presente artículo presentamos los resultados de un estudio descriptivo sobre los acogimientos en familia extensa en la ciudad de Barcelona, donde se recogen datos de los principales agentes implicados en este fenómeno. Desde la perspectiva de los estudios de la calidad de vida se analizan las percepciones, evaluaciones, y satisfacción expresada, por parte de los acogedores, los niños/as acogidos y los profesionales de los Equipos de Atención a la Infancia y Adolescencia (EAIA) que se encargan del estudio y seguimiento de estos acogimientos. La investigación presenta unos resultados acordes con los estudios que actualmente se realizan en este ámbito y sienta las bases para el despliegue futuro de programas dirigidos a los acogimientos en familia extensa

Un cadre conceptuel pour l'étude des castes en Inde : l'ethnographie Caste and kinship in Kangra réinterprétée dans une optique opérationnelle

Inspiré par la réflexion épistémologique de l'anthropologue Michel Verdon, ce mémoire propose un cadre conceptuel pour l'étude de l'organisation sociale des castes en Inde. L'ethnographie de Jonathan Parry, Caste and Kinship in Kangra, est analysée et réinterprétée dans un langage dit « opérationnel ». Les différentes approches des castes oscillent entre deux pôles théoriques opposés : l'idéalisme, représenté notamment par la démarche structuraliste de Louis Dumont, et le substantialisme, jadis adopté par les dirigeants coloniaux et incarné plus récemment dans les travaux de Dipankar Gupta. Toutes deux holistes, ces options conduisent pourtant à une impasse dans l'étude comparative de l'organisation sociale, car elles rendent les groupes « ontologiquement variables » et, par conséquent, incomparables. En repensant les prémisses sur lesquelles repose la conception générale de l'organisation sociale, un cadre opérationnel confère à la notion de groupe une réalité binaire, discontinue, évitant ainsi la variabilité ontologique des groupes et favorisant le comparatisme. Il rend également possible l'étude des rapports entre groupes et réseaux. La relecture de l'ethnographie Caste and Kinship in Kangra montre la pertinence d'une telle approche dans l'étude des castes. Le caractère segmentaire de ces dernières est remis en cause et l'autonomie des foyers, qui forment des réseaux d'alliances en matière d'activités rituelles, est mise de l'avant. Cette nouvelle description incite enfin à de nouvelles comparaisons.

Acogimiento en familia extensa: un estudio desde la perspectiva de los acogedores, de los niños y niñas acogidos y de los profesionales que intervienen. = Kinship foster care: a study from the perspective of the caregivers, the children and the child welfare workers

Desde hace aproximadamente dos décadas, en la mayoría de los países occidentales, los acogimientos en familia extensa han entrado a formar parte de los sistemas de protección infantil, siguiendo una evolución creciente en cuanto a número y peso especifico como recurso de acogimiento. Las investigaciones sobre este fenómeno son aún recientes y escasas como también lo son los programas dirigidos a esta población. En el presente artículo presentamos los resultados de un estudio descriptivo sobre los acogimientos en familia extensa en la ciudad de Barcelona, donde se recogen datos de los principales agentes implicados en este fenómeno. Desde la perspectiva de los estudios de la calidad de vida se analizan las percepciones, evaluaciones, y satisfacción expresada, por parte de los acogedores, los niños/as acogidos y los profesionales de los Equipos de Atención a la Infancia y Adolescencia (EAIA) que se encargan del estudio y seguimiento de estos acogimientos. La investigación presenta unos resultados acordes con los estudios que actualmente se realizan en este ámbito y sienta las bases para el despliegue futuro de programas dirigidos a los acogimientos en familia extensa