Much effort is currently directed towards generating and evaluating agents that target the individual components of the alloimmune response, with a view to promoting allograft survival accompanied by minimum side effects. Recently, there has been considerable interest in inhibiting individual cytokine/receptor interactions since they are key elements in pathways for differentiation of immune effector cells. This article examines the utility of targeting interactions of interleukin (IL)-15 with its receptor as a strategy for disabling the T-cell activation events following recognition of foreign major and minor histocompatibility antigens. Experimental evidence suggests that interrupting IL-15/IL-15R interaction may be of therapeutic value in preventing allograft rejection.
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J Immunother Cancer
January 2025
Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Background: A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit.
View Article and Find Full Text PDFZhonghua Fu Chan Ke Za Zhi
January 2025
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, State Key Laboratory of Female Fertility Promotion, National Clinical Research Center for Obstetric and Gynecologic Diseases, Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing100191, China.
To explore biomarkers for the efficacy of lymphocyte immunotherapy (LIT) treating women with unexplained recurrent spontaneous abortion (URSA). Serum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015. Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT.
View Article and Find Full Text PDFBiomolecules
January 2025
National Center for Global Health, Italian Institute of Health, 00161 Rome, Italy.
In chronic lymphocytic leukemia (CLL), natural killer (NK) cells show a dysfunctional phenotype that correlates with disease progression. Our aim was to restore NK cell functionality in CLL through a specifically targeted IL15-stimulating activity; IL15 targeting could, in fact, potentiate the activity of NK cells and reduce off-target effects. We designed and developed a cis-acting immunocytokine composed of an anti-CD56 single-chain Fragment variable (scFv) and IL15, labeled scFvB1IL15.
View Article and Find Full Text PDFBlood
January 2025
Hospital Santa Creu i Sant Pau, Barcelona, Spain.
CD30-directed CART cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, with a low proportion of durable responses. We have developed an academic CART30 cell product (HSP-CAR30) by combining strategies to improve performance. HSP-CAR30 targets a proximal epitope within the non-soluble part of CD30, and the manufacturing process includes a modulation of ex vivo T cell activation, as well as the addition of interleukin-21 to IL-7 and IL-15 to promote stemness of T cells.
View Article and Find Full Text PDFEpilepsia
January 2025
Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Objective: Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations.
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