Chimeric antigen receptor T-cell therapy for haematological malignancies: Insights from fundamental and translational research to bedside practice.

Autologous chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of lymphoid malignancies, leading to the approval of CD19-CAR T cells for B-cell lymphomas and acute leukaemia, and more recently, B-cell maturation antigen-CAR T cells for multiple myeloma. The long-term follow-up of patients treated in the early clinical trials demonstrates the possibility for long-term remission, suggesting a cure. This is associated with a low incidence of significant long-term side effects and a rapid improvement in the quality of life for responders. In contrast, other types of immunotherapies require prolonged treatments or carry the risk of long-term side effects impairing the quality of life. Despite impressive results, some patients still experience treatment failure or ultimately relapse, underscoring the imperative to improve CAR T-cell therapies and gain a better understanding of their determinants of efficacy to maximize positive outcomes. While the next-generation of CAR T cells will undoubtingly be more potent, there are already opportunities for optimization when utilizing the currently available CAR T cells. This review article aims to summarize the current evidence from clinical, translational and fundamental research, providing clinicians with insights to enhance their understanding and use of CAR T cells.

Advancing CAR T-cell therapies: Preclinical insights and clinical translation for hematological malignancies.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in achieving durable and potentially curative responses in patients with hematological malignancies. CARs are tailored fusion proteins that direct T cells to a specific antigen on tumor cells thereby eliciting a targeted immune response. The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into robust clinical efficacy has shown modest outcomes in both clinical trials and real-world scenarios. Therefore, the assessment of CAR T-cell functionality through rigorous preclinical studies plays a pivotal role in refining therapeutic strategies for clinical applications. This review provides an overview of the various in vitro and animal models used to assess the functionality of CAR T-cells. We discuss the findings from preclinical research involving approved CAR T-cell products, along with the implications derived from recent preclinical studies aiming to optimize the functionality of CAR T-cells. The review underscores the importance of robust preclinical evaluations and the need for models that accurately replicate human disease to bridge the gap between preclinical success and clinical efficacy.

Vaccines for leishmaniasis and the implications of their development for American tegumentary leishmaniasis.

The leishmaniases are a collection of vector-borne parasitic diseases caused by a number of different Leishmania species that are distributed worldwide. Clinical and laboratory research have together revealed several important immune components that control Leishmania infection and indicate the potential of immunization to prevent leishmaniasis. In this review we introduce previous and ongoing experimental research efforts to develop vaccines against Leishmania species. First, second and third generation vaccine strategies that have been proposed to counter cutaneous and visceral leishmaniasis (CL and VL, respectively) are summarized. One of the major bottlenecks in development is the transition from results in animal model studies to humans, and we highlight that although American tegumentary leishmaniasis (ATL; New World CL) can progress to destructive and disfiguring mucosal lesions, most research has been conducted using mouse models and Old World Leishmania species. We conclude that assessment of vaccine candidates in ATL settings therefore appears merited.