P1, N=50, Recruiting, Dana-Farber Cancer Institute | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
18 days ago
Enrollment open • Trial completion date • Trial primary completion date
Lastly, TCR-NKs are not activated when co-cultured with normal cells, displaying a safe profile. Combining the innate cytotoxicity of NKs with MAGE-A4-specific targeting of an affinity-enhanced TCR, results in a potent and safe cellular product representing a promising and novel therapeutic off-the-shelf paradigm for the treatment of many solid cancers.
A bifunctional PROTAC, namely dSLC7A11, ws designed by conjugating the SLC7A11 inhibitor sulfasalazine to the CRBN ligand pomalidomide via an alkyl linker. Notably, dSLC7A11 exhibited superior antitumor efficacy over sulfasalazine alone, and achieved an effect of suppressing tumor growth by >65% in vivo. This study presented a SLC7A11-targeting PROTAC that disrupts the cellular antioxidant defense system, thus establishing a novel PROTAC-based approach for potent ferroptosis induction in cancer therapy.
21 days ago
Journal
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CRBN (Cereblon) • GPX4 (Glutathione Peroxidase 4) • SLC7A11 (Solute Carrier Family 7 Member 11)
Analysis of the FAERS database revealed that the PD-L1 inhibitor durvalumab is significantly associated with TB-related adverse events (reporting odds ratio = 7.81; 95% CI: 4.43-13.78; P = 1.10×10-18)...In silico drug prediction and molecular docking suggested several PD-L1-modulating compounds, including ruthenium, pomalidomide, zidovudine, and lycorine...Together, our findings define a mechanistic axis in CD14- CD16+ monocytes that underpins early TB control and is vulnerable to PD-L1 blockade. Collectively, these findings align with the established notion that assessing latent tuberculosis infection before initiating immune-modulating therapies is essential for minimizing reactivation risk, and propose tractable molecular targets for preventing TB reactivation in immunocompromised hosts.
26 days ago
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD14 (CD14 Molecule) • LMO2 (LIM Domain Only 2)
P1, N=160, Active, not recruiting, D2M Biotherapeutics Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Mar 2026
27 days ago
Enrollment closed • Trial primary completion date • First-in-human
Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53-/- myeloma support its clinical efficacy and application in the del(17p) and TP53-/- patient population.Trial registration NCT03151811, registration 2017-05-09.
Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide degrade IKZF1/3 and are combined with other therapies to treat hematologic malignancies, including multiple myeloma and non-Hodgkin lymphoma. Molecular docking studies suggested that DIX-01 may form stable ternary complexes with CRBN-IKZF1 and CRBN-GSPT1, providing a structural basis for its dual-target degradation activity. Furthermore, DIX-01 significantly inhibited tumor growth in a zebrafish xenograft model transplanted with human acute myeloid leukemia cells (MV4-11), supporting its potential as a therapeutic agent for hematologic malignancies.
1 month ago
Journal
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IKZF1 (IKAROS Family Zinc Finger 1) • CRBN (Cereblon) • GSPT1 (G1 To S Phase Transition 1)