Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome.

Background: 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described.

Methods: We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied.

Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach.

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes.

Evidence of clinical efficacy of a first generation CD19 CAR T cell in B cell malignancies.

The persistence and reactivity of CAR T cells were enhanced by adding co-stimulatory domains, which is the basis of currently approved CAR-T cell therapies. However, this comes at the expense of increasing toxicities from the strong cytokine release effect. This is the first report from anti-CD19 CAR-T cell therapy with a single activation domain to show a favourable safety profile and clinical efficacy with two patients who achieved durable responses up to 28 months in a cohort with heavily pretreated B cell malignancies.

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma.

Nonselected autologous tumor-infiltrating lymphocytes (TILs) may provide advantages over other treatments for solid tumors, including checkpoint inhibitor-refractory melanoma. This retrospective analysis reports a single-center experience of nonselected autologous TILs derived from digested tumors for compassionate use treatment of advanced cutaneous melanoma, including after programmed cell death protein 1 (PD-1) inhibition. Patients with histologically confirmed metastatic cutaneous melanoma and no standard-of-care treatment options underwent tumor resection for TIL product manufacturing.

Borderline personality features among individuals at clinical high risk for psychosis (CHR-P): A brief report.

Aim: This exploratory study reports on borderline symptomatology within a sample of individuals at clinical high risk for psychosis (CHR-P) through a validated, self-report instrument, the short version of the Borderline Symptom List (BSL-23).

Methods: The sample consisted of 44 help-seeking CHR-P youth (ages 14-29 years) who completed an initial evaluation at a specialized clinic for psychosis-risk.

Results: The mean BSL-23 score was 1.

Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care.

Purpose: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care.

Methods: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments.

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity.

The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5 malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion.

Definition and application of good manufacturing process-compliant production of CEA-specific chimeric antigen receptor expressing T-cells for phase I/II clinical trial.

Adoptive cell therapy employing gene-modified T-cells expressing chimeric antigen receptors (CARs) has shown promising preclinical activity in a range of model systems and is now being tested in the clinical setting. The manufacture of CAR T-cells requires compliance with national and European regulations for the production of medicinal products. We established such a compliant process to produce T-cells armed with a first-generation CAR specific for carcinoembryonic antigen (CEA).

The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens.

Human peripheral blood lymphocytes can be transduced to express antigen-dependent CD3zeta chimeric immune receptors (CIRs), which function independently of the T-cell receptor (TCR). Although the exact function of these domains is unclear, previous studies imply that an extracellular spacer region is required for optimal CIR activity. In this study, four scFvs (in the context of CIRs with or without extracellular spacer regions) were used to target the human tumor-associated antigens carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), the oncofetal antigen 5T4, and the B-cell antigen CD19.

Gene therapy of patient-derived T lymphocytes to target and eradicate colorectal hepatic metastases.

Purpose: The overall aim of this study was to develop a novel treatment for colorectal cancer based on the use of gene therapy. Genetic modification of T lymphocytes has been used to specifically target and kill tumor cell lines directly. To test the efficacy of this method with clinically relevant materials, this study investigated the potential of T lymphocytes derived from patients with advanced colorectal disease to target autologous primary tumor material.

Primary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune receptors.

Antigen-specific T lymphocytes are attractive as potential anticancer agents. The generation of large numbers of antigen-specific T cells is possible through the use of gene therapy to express targeting receptors on the T lymphocyte. Activated T lymphocytes were transduced to express carcino-embryonic antigen or neural cell adhesion molecule targeted CD3zeta chimeric immune receptors.