Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers.

Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers.

Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment. To allow stratification of patients according to tumor GD2 expression, we established and validated immunofluorescence detection of GD2 on paraffin-embedded tumor tissues.

Fully closed and automated enrichment of primary blood dendritic cells for cancer immunotherapy.

Dendritic cell (DC) vaccination is a promising approach to induce tumor-specific immune responses in cancer patients. Until recently, most DC vaccines were based on in vitro-differentiated monocyte-derived DCs. However, through development of efficient isolation techniques, the use of primary blood dendritic cell subsets has come within reach.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens.

Immunological responses to adjuvant vaccination with combined CD1c myeloid and plasmacytoid dendritic cells in stage III melanoma patients.

We evaluated the immunological responses of lymph-node involved (stage III) melanoma patients to adjuvant dendritic cell vaccination with subsets of naturally occurring dendritic cells (nDCs). Fifteen patients with completely resected stage III melanoma were randomized to receive adjuvant dendritic cell vaccination with CD1c myeloid dendritic cells (cDC2s), plasmacytoid dendritic cells (pDCs) or the combination. Immunological response was the primary endpoint and secondary endpoints included safety and survival.

Blood DCs activated with R848 and poly(I:C) induce antigen-specific immune responses against viral and tumor-associated antigens.

Monocyte-derived Dendritic cells (DCs) have successfully been employed to induce immune responses against tumor-associated antigens in patients with various cancer entities. However, objective clinical responses have only been achieved in a minority of patients. Additionally, generation of GMP-compliant DCs requires time- and labor-intensive cell differentiation.

Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer.

Background: Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c myeloid dendritic cells (mDCs; cDC2) and plasmacytoid DCs (pDCs).

Methods: In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs.

Toward Empirical Evidence for Teachers' Mental Representations of Dyadic Relationships With Students: Two Priming Experiments.

The attachment-based perspective on teacher-student relationships assumes that teachers internalize experiences with specific students into mental representations of dyadic relationships. Once activated, mental representations are believed to influence teachers' affective and cognitive social information processing. Two priming experiments with 57 elementary school teachers were conducted to test these assumptions.

The Implementation of Extended Examination Duration for Students With ADHD in Higher Education.

Objective: Recently, research indicated that extended examination duration was perceived as effective by students with ADHD. However, the objective effectiveness of this accommodation has not been researched extensively. This study addresses this gap in literature.

Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells.

Purpose: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c(+) myeloid DCs, naturally circulating in the blood.

Experimental Design: Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c(+) myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100.

First-grade retention in the Flemish educational context: Effects on children's academic growth, psychosocial growth, and school career throughout primary education.

This study examined the effects of first-grade retention on children's academic growth, psychosocial growth, and future school career by following a cohort of first graders until the start of secondary school. The study took place in the Flemish educational context where primary school students are taught in uniform curricular year groups; the same curricular goals are set for all students, irrespective of ability; and grade retention is used as the main way to cater for students not reaching these goals. Propensity score stratification was used to deal with selection bias.

Factorial validity of the Chedoke-McMaster Attitudes towards Children with Handicaps Scale (CATCH).

The Chedoke-McMaster Attitudes towards Children with Handicaps Scale (CATCH) has been developed to measure the attitudes of children toward peers with disabilities. The present study aims to evaluate the factorial validity of the CATCH in a sample of 2396 students in 7th grade, including 179 students with disabilities and 2217 typically developing students. Each classroom included at least one student with a disability.

The role of attention in the affective life of people with severe or profound intellectual disabilities.

Although it is shown that attention plays an important role both in the onset and in the regulation of emotions in people without disabilities there is no information about how attention is related to emotions in people with severe or profound intellectual disability (ID). Therefore, in our study, we investigated the role of attention in the onset and regulation of the emotions of persons with severe or profound ID. We presented 27 participants with 4 staff-selected negative and 4 staff-selected positive stimuli.

Loneliness among students with special educational needs in mainstream seventh grade.

The goals of this study were twofold. The first aim was to explore loneliness prevalence in typically developing students, students with ASD and students with motor and/or sensory disabilities in mainstream 7th grade in Belgium. The second aim was to explore the relations between number of friends, friendship quality, social self-concept on the one hand and loneliness on the other for each of these three groups, and to compare them across groups.

The tell-tale: what do heart rate; skin temperature and skin conductance reveal about emotions of people with severe and profound intellectual disabilities?

Identifying emotions in people with severe and profound intellectual disabilities is a difficult challenge. Since self-reports are not available, behaviour is the most used source of information. Given the limitations and caveats associated with using behaviour as the sole source of information about their emotions, it is important to supplement behavioural information with information from another source.

The attitudes of Belgian adolescents towards peers with disabilities.

This study aimed to explore Belgian adolescents' attitudes towards peers with disabilities and to explore factors associated with these attitudes. Based on the theory of persuasive communication, this study focused on receiver variables (the "whom"), characteristics of students with disabilities ("concerning who") and channel ("how"). An online survey was created and published on several popular websites for youngsters.

Psychometric evaluation of the Dutch version of the Mood, Interest and Pleasure Questionnaire (MIPQ).

Recently, several instruments have been developed to measure the subjective component of the quality of life (QOL) of people with profound intellectual and multiple disabilities (PIMD). A next step, however, must be the further validation of these instruments. The present study aimed at evaluating the psychometric properties of one of these instruments, the Dutch version of the Mood, Interest and Pleasure Questionnaire (MIPQ).

What makes them feel like they do? Investigating the subjective well-being in people with severe and profound disabilities.

Background: Because of the problems measuring subjective well-being in people with severe and profound intellectual disabilities, there are no studies to date which explore the factors contributing to the subjective well-being in these groups. We wanted to explore the client and service characteristics contributing to the subjective well-being of persons with severe and profound intellectual disabilities, as measured by the MIPQ (Ross & Oliver, 2003).

Materials And Methods: The MIPQ was completed for 360 persons with severe or profound intellectual disabilities by a member of the direct support staff.

Measuring the quality of life of people with profound multiple disabilities using the QOL-PMD: first results.

The present study focused on the objective components of quality of life (QOL) of people with profound multiple disabilities (PMD). More specific, we aimed at evaluating different dimensions of QOL of people with PMD and investigating the association between their QOL and several personal (age, gender, intellectual capabilities, motor limitations, sensory limitations, physical and mental health status) as well as setting characteristics (location of the setting, type of setting, size of the setting, group size, group composition, staffing level and staff turnover). As a measure of the QOL of people with PMD we used the QOL-PMD, a questionnaire that we specifically developed for this purpose.

Psychometric evaluation of a questionnaire to measure the quality of life of people with profound multiple disabilities (QOL-PMD).

Because of a shortage of valid instruments to measure the QOL of people with profound multiple disabilities (PMD), the QOL-PMD was developed. In the present study, possibilities for item reduction as well as the psychometric properties of the questionnaire were examined. One hundred and forty-seven informants of people with PMD participated in the study.

Quality-enhancing interventions for people with profound intellectual and multiple disabilities: a review of the empirical research literature.

Background: This study provides an overview of empirical research on the effectiveness of quality-enhancing interventions for people with profound intellectual and multiple disabilities (PIMD).

Method: Through computerised searches of the PsycINFO and ERIC databases, and using several search criteria specifically relating to the target group and to the subject of this review, 16 studies were identified.

Results: The interventions described are targeted at the physical and material well-being, emotional well-being, social interactions, choices, and personal development of individuals with PIMD, but do not address community participation and rights.

Identifying expressions of pleasure and displeasure by persons with profound and multiple disabilities.

Background: The aim of this study was to explore a procedure for drafting individualised profiles of how people with profound multiple disabilities express pleasure and displeasure.

Method: There were 6 participants with profound multiple disabilities. The procedure involved an observational analysis of videotaped critical incidents by a researcher and a questionnaire for parents and support workers.