Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.

Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in vitro and in vivo efficacy in cell line- and human-derived AML models with minimal off-target toxicity toward relevant healthy human tissues. This provides a strong rationale for further clinical development.

Turkish Version of Structured Interview of Psychosis-Risk Syndromes (SIPS) and Proposal of a Brief Version of SIPS as a Pretest Risk Enrichment.

Introduction: The Structured Interview of Psychosis Risk Syndromes (SIPS) was created to identify patients with Clinical High Risk for psychosis (CHR). This study aimed i) to translate and validate the Scale of Prodromal Syndromes (SOPS) in Turkish adolescents, ii) to explore the factor structure of the SIPS/SOPS in the adolescent population, especially focusing on those under the age of 15, iii) to generate a brief version of SIPS (SIPS-B). Methods: A total of 150 adolescents aged between 12 and 18 years, were consecutively interviewed using SIPS/SOPS. Patients with psychotic syndrome (n=20), psychosis risk syndrome (PRS) (n=59), and clinical controls (CC) (n=71) were included in the study. Results: Principal component analysis (PCA) yielded three latent factors, explaining 62.7% of the total variance in the whole clinical sample, including positive symptom factor, disorganized symptom factor, and negative symptom factor. The area under curve calculated in ROC analyses involving PRS and CC supported the four-item form of the SIPS-B (optimal cut-off=12.5, sensitivity=87%, specificity=80%). Conclusion: Our study results support the notion that the Turkish translation of SIPS/SOPS meets the reliability and validity criteria in Turkish adolescents. The SIPS-B could aid clinicians in their routine clinical practice to expedite referral procedures.

CAR T cell therapy in solid tumors: a short review.

Chimeric antigen receptor (CAR) T cell therapy has been established in the treatment of hematological malignancies. However, in solid tumors its efficacy remains limited. The aim of this article is to give an overview of the field of cell therapy itself, to introduce the underlying concepts of CAR T cell-based treatment approaches and to address its limitations in advancing the treatment for solid malignancies.

T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours.

The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.