IL2RA expression

Furthermore, a modified huCD39 mAb-secreting CAR-T cell has been generated, exhibiting superior efficacy against ovarian cancer. This provides a promising strategy for optimizing immunotherapies in ovarian cancer and potentially other malignancies.

This research shows the potential for a non-genetic method for redirecting cytotoxic immune cells as a feasible and effective approach for tumor-targeted cell immunotherapy.

Differences in common γ-chain cytokine receptor expression between PD-1+ and TIM-3+ T cells may reflect functional dissimilarity of these cell subsets. Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+ T cells but may raise the possibility of immune-mediated adverse events.

Our preliminary data suggest that the immune-related markers signature in the healthy peritumoral mucosa might be useful for predicting relapse after adjuvant therapy in rectal cancer patients. Moreover, relapsing patients showed lower stimulation of macrophages and lymphocytes, thus suggesting that impaired immune surveillance might influence adjuvant therapy outcomes. Sampling healthy mucosa might help the decision-making about adjuvant therapy after surgery for rectal cancer.

P3, N=120, Recruiting, International Extranodal Lymphoma Study Group (IELSG) | Not yet recruiting --> Recruiting

CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.

Signaling through the high-affinity IL-2R also reinvigorates CD8+ exhausted T (Tex) cells in response to checkpoint blockade. We consider the molecular underpinnings reflecting how IL-2R signaling impacts these various T cell subsets and the implications for enhancing IL-2-dependent immunotherapy of autoimmunity, other inflammatory disorders, and cancer.

There was a strong correlation between CD4+ T cells as well as total T cells in the pre-therapy TME, and an increase in NK cell CD16 and CD25 expression following RTX. We conclude that T cell help in the TME enhances RTX-mediated NK cell viability and ADCC.

The use of chemo-immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl-2 inhibitors (Bcl-2i). However, the optimal sequence of the different treatments remains to be determined.

to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

Using cell-cell communication network inference and pathway analysis on single cell RNA sequencing data, we also highlighted key components of the immunological synapse occurring between T cells and the stimulatory MoDCs together with downstream signaling pathways involved in CD4 and CD8 T cells activation. These results provide a deep understanding of the kinetics of the MLR assay for CD4 or CD8 T cells and may allow to better characterize compounds impacting MLR and eventually identify new strategies for immunotherapy in cancer.

P1, N=12, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

P=N/A, N=60, Recruiting, National Cancer Institute, Egypt | Not yet recruiting --> Recruiting

The results demonstrated that the third-generation anti-VEGFR2 nanobody-based CAR T cell with a long spacer had a superior function and potentially could be a better candidate for solid tumor treatment.

P=N/A, N=53, Completed, Boston Medical Center | Active, not recruiting --> Completed

SM patients present with multiple underlying symptoms, within various disease subtypes that are difficult to diagnose in a timely manner. As a result, many patients do not receive active drug therapy for their disease. Therefore, greater disease awareness is required as well as new tools for earlier disease detection.

This finding was reproduced in AML without a core-binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.

The anti-lymphoma efficacy of engager-CAR T cell therapy will be further evaluated in our well-established unique PDX model for MCL. In summary, we have successfully generated a CD20-directed bispecific T-cellengaging antibody and CD20-BiTE engager-T cells that could be combined with CAR T cell therapy, which was demonstrated effective in overcoming tumor antigen escape and resistance to current CD19-CAR T cell therapy in MCL.

Two study arms shows similar data respect to clinical outcome. Patients infused with IL-15-stimulated NK cells showed similar toxicity to the alloreactive NK group. According to dose escalation, we observed no association between increased toxicity and increased number of infused NK cells.

The patient started hematological follow up, treatment with hydroxyurea and transfusion support for LMMC diagnosis. Midostaurin is a TKI effective against KITD816V with an ORR of 60% in aggressive SM. Although midostaurin represents the most potent agent available for SM patients, other medications are under investigation to overcome resistance due to D816V-mutated variant of KIT.

Strong inflammatory infiltrate in the tumor microenvironment is correlated with an invasive phenotype. CD25 and p-NFkB levels were statistically significantly overexpressed in cancer cells.

In conclusion, this study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.

Our findings suggest that DNTs attenuate acute aGVHD by affecting the proliferation and activation of CD4+T cells via the CD25-JAK-STAT pathway, which is important to the prevention and management of aGVHD.

Equal efficacy is observed in U266 cells resistant to Bortezomib and BCMA KO U266 cells...Our work supports the rationale development of ILT3 CAR-T cell therapy as a viable therapeutic approach for MM patients especially high-risk patients. Ongoing studies are investigating the functional role of LILRB4 in mediating the cross-talk between MM ad immune cells.

Here we show the experimental development of a third-generation CAR-NK therapy strategy against the CD25 based on the scFV of the clinically approved monoclonal humanized antibody, Basiliximab... We show here for the first time the potential use of an NK cell-mediated CAR therapy strategy targeting CD25 which has been shown to be upregulated in CML blast crisis. The experimental data show a significantly increased and selective in vitro and in vivo cytotoxicity of CD25 CAR-NK92 cells against CD25-expressing leukemia cells as compared to WT-NK92 cells. These results suggest that targeting CD25 by a CD25 CAR based on Basilixiamb's scFV might be an interesting tool in BC-CML and in all acute leukemias overexpressing CD25.

SAR442257 also induced CD25 and CD69 expression on normal T-cells suggesting efficient T-cell activation, (data not shown). Conclusion Altogether, this study shows that 1) most PTCL cells express at least CD28 or CD38, and 2) SAR442257 can efficiently kill malignant PTCL cells, while ensuring effective T-cell activation; In view of these results, clinical investigation of SAR442257 in PTCL is warranted.

Ex vivo drug sensitivity analyses support combinations of CD25-targeting agents with FLT3 inhibitors, as well as venetoclax. Additional work to evaluate these and other combinations using functional assays is warranted.

In syngeneic tumor experiments with B16 melanoma expressing ovalbumin (B16-Ova), Pdcd1f/fCD11cCre mice and Pdcd1f/fClec9Cre mice similarly had greater tumor sizes and weights compared to their control counterparts. These results indicate that selective ablation of PD-1 in DCs cells confers a more immunosuppressive tumor microenvironment by promoting T regulatory cell expansion and diminishing CD8+ T effector cell activation compromising anti-tumor responses.

Metformin pre-treatment elevates CAR-T cytotoxicity following chronic antigen stimulation, but only when coupled with AMPKγ2 overexpression. This combination is what we predict will improve the function of CD19-CAR T cells in our murine xenograft leukemia model and human samples.

Results demonstrated that the developed co-culture platform allows precise control over culture conditions, ensuring culture of accurate ratios of highly complex cell populations. The viability of primary cells in the device guaranteed functional relevance of the cytotoxicity assays for up to a 96-hour timepoint. Strong CAR-T-mediated cell killing was observed, with a dose-dependent effect depending on the co-culture's relative CAR-T content.

P=N/A, N=60, Not yet recruiting, National Cancer Institute, Egypt

P3, N=120, Not yet recruiting, International Extranodal Lymphoma Study Group (IELSG) | Trial completion date: Sep 2028 --> Feb 2029 | Initiation date: Sep 2023 --> Feb 2024 | Trial primary completion date: Sep 2028 --> Feb 2029

In most cancers, the results indicate that there is no link between CCDC25 and prognosis. However, CCDC25 can be targeted for therapeutic purposes concerning metastasis and immune infiltration.

P=N/A, N=200, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Aug 2023 --> Aug 2024

P=N/A, N=150, Recruiting, The First Affiliated Hospital of Soochow University | Not yet recruiting --> Recruiting

Moreover, we find that blocking the specific receptor (PD-1) using antibodies significantly relieves the S. aureus-imposed inhibition. Our findings suggest that therapeutically targeting PD-1 is a possible future strategy for treating certain antibiotic-resistant staphylococcal infections.

HDL levels increased after the onset of GvHD and were elevated in patients, who relapsed at a later time point. Therefore, HDL might not be important for driving GvHD development and may be induced by steroid administration after GvHD onset. However, T-cells can be affected by high HDL levels, which may have a long-term impact on the therapeutic outcome of these patients with respect to relapse.

Target cell-restricted lysis of AML cell lines and primary AML patients’ samples by 8H8-SDIE was potently induced in Europium and FACS-based cytotoxicity assays, while iso-SDIE treatment did not induce lysis of leukemic cells. Conclusions Taken together, we here introduce a novel attractive immunotherapeutic compound potently inducing NK cell anti-leukemic reactivity as a beneficial treatment option for AML.