Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn-humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation.

We demonstrate that lena can augment the hRT-induced abscopal effect in mouse solid tumor models in a CD8 T cell- and IFN-I-dependent manner, correlating with enhanced anti-tumor CD8 T cell immunity, DC cross-presentation, and TA-HEC numbers. Our findings may be helpful for the planning of clinical trials in (oligo)metastatic patients.

P2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2028

P2, N=30, Recruiting, St. Joseph's Hospital and Medical Center, Phoenix | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

P3, N=2, Completed, Seoul National University Hospital | Unknown status --> Completed | N=30 --> 2

P2, N=48, Completed, IRCCS San Raffaele | Unknown status --> Completed

P=N/A, N=38, Completed, Qianfoshan Hospital | Recruiting --> Completed | N=60 --> 38 | Trial completion date: May 2024 --> May 2023 | Trial primary completion date: Dec 2023 --> May 2023

Complete remission was maintained for over one year with lenalidomide maintenance therapy. A solitary IgH::MYC chromosomal translocation is extremely rare in multiple myeloma and may be associated with high tumor proliferative capacity, multiple extramedullary lesions, and poor prognosis. Combined therapeutic modalities with novel and conventional chemotherapy and radiation might be a promising treatment strategy for patients with this type of multiple myeloma.

P3, N=226, Active, not recruiting, National Cancer Institute (NCI)

P3, N=525, Active, not recruiting, National Cancer Institute (NCI)

CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

P1, N=22, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Aug 2021 --> Aug 2024

Furthermore, several other strains of NDV also exhibited inhibitory activity. The current study reveals that NDV can modulate the intensity of the innate‍‒‍adaptive immune cell crosstalk critically toward viral invasion improvement, highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

P3, N=306, Active, not recruiting, National Cancer Institute (NCI)

P3, N=460, Active, not recruiting, National Cancer Institute (NCI)

PI3K activator SC79 significantly restored reduced cell proliferation, migration and invasion along with elevated cell cycle arrest and apoptosis caused by lenalidomide and gefitinib cotreatment. In conclusion, lenalidomide and gefitinib synergistically suppressed LUAD progression and attenuated gefitinib resistance by upregulating ADRB2 and inactivating the mTOR/PI3K/AKT signaling pathway in lung adenocarcinoma.

Furthermore, we observed that patients who underwent lenalidomide-comprising induction therapy had significantly shorter progression-free survival when their samples were CDK6 positive. These data support that CDK6 protein expression is a marker for aggressive and drug-resistant disease and describes a potential drug target in MM.

The advanced MM stage, depth of response, and lower relative count of circulating E-MDSCs at the engraftment were independent risk factors associated with a lower progression-free survival. The obtained data allow us to hypothesize that MDSCs may play a positive role at the stage of leukocyte recovery by ameliorating the long-term anti-tumor response in MM.

In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.

P2/3, N=57, Active, not recruiting, Lawson Health Research Institute | Recruiting --> Active, not recruiting | N=86 --> 57 | Trial completion date: Jul 2026 --> Sep 2024 | Trial primary completion date: Dec 2024 --> Dec 2023

P1/2, N=68, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2023 --> Sep 2024

P2, N=17, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=190 --> 17

P2, N=54, Active, not recruiting, Amgen | Trial completion date: Dec 2025 --> Oct 2024

P1/2, N=52, Active, not recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2025 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=300, Not yet recruiting, University Hospital, Caen

Among the synthesized compounds, the lenalidomide-based PROTAC 42i was the most promising...42i selectively degraded ATR through the proteasome, dependent on the E3 ubiquitin ligase component cereblon, and without affecting the associated kinases ATM and DNA-PKcs. 42i may be a promising candidate for further optimization and biological characterization in various cancer cells.

The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

P2, N=75, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Dec 2023

p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. The rate of vacuole dissolution (i.e., LEL fission), following the removal of apilimod, was also significantly reduced in cells treated with BIRB-796, a structurally unrelated p38 MAPK inhibitor. Thus, our studies indicate that pyridinyl imidazole p38 MAPK inhibitors induce cytoplasmic vacuolation through the combined inhibition of both PIKfyve and p38 MAPKs, and more generally, that p38 MAPKs act epistatically to PIKfyve, most likely to promote LEL fission.

The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

P=N/A, N=110, Recruiting, Celgene | Trial completion date: May 2023 --> Mar 2025 | Trial primary completion date: Sep 2022 --> Mar 2025

P1, N=55, Completed, RANI Therapeutics | Active, not recruiting --> Completed

All cases and controls had a primary diagnosis of MM and received len-post-autoHCT with melphalan; sequencing was performed on an aliquot of the apheresis product or peripheral blood sample that was collected before autoHCT for MM. Our results demonstrate an interesting risk variant for ALL, and potentially AML/MDS, SPM emerging in the setting of len-post-autoHCT. It is important to identify patients at higher risk of SPMs for survivorship screening, and to better understand the pathogenesis of acute leukemia SPMs associated with lenalidomide maintenance.

Moreover, ablation of host MAVS sensitized tumors to immunotherapy and attenuated radiation resistance, thereby facilitating the maintenance of effector CD8 T cells. These findings demonstrate that the host MAVS pathway acts as an immune regulator of DC-driven antitumor immunity and support the development of immunotherapies that antagonize MAVS signaling in DCs.

P3, N=384, Active, not recruiting, Biocon Biologics UK Ltd | Trial completion date: Oct 2023 --> May 2024

P1, N=55, Active, not recruiting, RANI Therapeutics | Not yet recruiting --> Active, not recruiting | Trial completion date: Apr 2024 --> Nov 2023 | Trial primary completion date: Apr 2024 --> Nov 2023

Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.

Moreover, the protective effect of CpG stimulation, and to a lesser extent of TLR3 and TLR7/8, and the role of IL-12 in this protection were confirmed in a model of early mesothelioma AB1 cell growth. These results suggest that modulation of the mouse immune microenvironment by ligation of innate receptors deeply modifies the efficiency of cancer immunosurveillance through the secretion of IL-12, which may at least partly explain the inhibitory effect of previous infections on the prevalence of some cancers.

Future experiments will assess the functionality of CD39 + CD8 + T-cells using ex vivo cytotoxicity assays. Data generated in this study will provide novel information on the mechanism of CD39 induction and its effect on CD8 + T-cell function, which can be exploited to improve future cancer therapies.

Likewise, Ad-IL-12/GPC3 vaccine also effectively inhibited lung tumor growth or metastasis by enhancing CD8 DCs-mediated multifunctional CD8 T cell immune responses in the lung metastasis model. Therefore, these results indicate that IL-12 combined with Ad-GPC3 vaccine co-immunization might provide a promising therapeutic strategy for HCC patients.

Therefore, we believe that codelivery of siRNA and pIL-12 can effectively inhibit hepatitis B virus, reverse virus-induced immunosuppression, reactivate antiviral immunity, and hinder the progression of HBV-induced hepatocellular carcinoma. This investigation provides a promising approach for the synergistic treatment of HBV infection.