Together, we established a proof of concept for PROTAC in the DC vaccine design by linking E3 ligase to a protein model antigen, which can be readily replaced with other identified pathogenic antigens to elicit robust cytotoxic immune responses against tumors or viral diseases, and thus has serious implications in the clinics.

P2, N=26, Completed, AIDS Malignancy Consortium | Trial completion date: Jan 2026 --> Apr 2025 | Active, not recruiting --> Completed

While novel agents continue to expand treatment options, ASCT2 remains a viable therapeutic strategy in appropriately selected patients, especially those with durable responses to prior therapy.

In the present study, we established a modular synthetic platform to systematically generate a set of PROTAC degrader candidates consisting of the CK1δ-specific inhibitor scaffold, alkyl and PEG linker motifs with various lengths, and Cereblon (CRBN)-engaging pomalidomide and thalidomide derivatives as E3 ligase binders. The most potent PROTAC P1d inhibits the phosphorylation of downstream substrates through CK1δ/ε degradation. We establish the requirement of CUL4ACRBN and the proteasome for the P1d-mediated degradation of CK1δ/ε.

We previously reported that a high Kyn/Trp ratio was associated with poor prognosis in lenalidomide-treated refractory/relapsed MM patients and that IDO expression in stromal cells was upregulated by co-culture with MM cells...These results suggest that the JAK-STAT1-NF-κB-IRF1 signaling pathway may be involved in IDO upregulation. JAK inhibitors may improve the TME in MM and positively influence immunotherapy outcomes.

This study identifies a novel signaling cascade whereby TMZ-resistant GBM secretes COL6A1 to activate an IKZF1-UBD axis in ECs, disrupting blood vessel integrity and facilitating MDM infiltration. Our findings delineate the pivotal mechanism by which tumor cells engage ECs to drive MDM infiltration - a linchpin part of the positive-feedback loop that couples TMZ resistance to MDM influx. Targeting IKZF1 with LEN represents a promising strategy for restoring endothelial barrier function, reducing MDM infiltration, and enhancing chemosensitivity in GBM.

Mechanistically, TPM3-TRKA degradation by compound 9 was dependent on CRBN-mediated polyubiquitination and proteasomal degradation; accordingly, it was hindered by inhibitors of the proteasome (MG132) or Cullins (MLN4924), by dominant negative Cullin 4A mutant, and by free pomalidomide. Finally, a compound 9 derivative, compound 20, induced in vivo degradation of TMP3-TRKA in KM12 cells mouse xenografts. In conclusion, our study indicated that PROTAC-mediated degradation is an efficient strategy to intercept RET and TRKA oncogenic signaling.

We report on a series of three patients diagnosed with secondary acute lymphoblastic leukemia (sALL) following treatment for multiple myeloma (MM) where serial, commercially available, next-generation sequencing (NGS) based tracking of measurable residual disease (MRD) using the clonoSEQ assay provided valuable clinical insight. Each of the patients in this series had been treated for their MM with regimens that had included autologous stem cell transplantation following high dose melphalan chemotherapy and had been on maintenance treatment with the immunomodulatory drug lenalidomide for at least one year.

Given the immune-enhancing effects and excellent safety profile, pomalidomide should be further investigated as an immune-enhancing strategy for an HIV cure.

In conclusion, encouraging activity was seen with blinatumomab and lenalidomide in heavily pre-treated R/R B-NHL. NCI Protocol # 9924.

Stratifying patients with MM based on myeloma cell maturity provides meaningful information for choosing the best treatment strategy and improving patient outcomes.