SS1(dsFv)-PE38 / AstraZeneca, National Cancer Institute - LARVOL DELTA

The conserved C-terminus of Sss1p is required to maintain the ER permeability barrier. (PubMed, J Biol Chem) - "The ER stress response was found to be constitutively induced in two temperature sensitive sss1 mutants (sss1 ) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1 cells to grow at 37C suggests the ER permeability barrier to be compromised in these mutants.  We propose the extreme C-terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier."

Journal • Targeted Protein Degradation

Normal levels of ribosome-associated chaperones cure two groups of [PSI+] prion variants. (PubMed, Proc Natl Acad Sci U S A) - "Ssz1p is degraded in zuo1Δ [psi-] cells, but not if the cells carry any of several [PSI+] variants. Our results imply that prions arise more frequently than had been thought but the cell has evolved exquisite antiprion systems that rapidly eliminate most variants."

Journal

Phase 1 study of the immunotoxin LMB-100 in patients with mesothelioma and other solid tumors expressing mesothelin. (PubMed, Cancer) - "The MTD for single-agent LMB-100 was found to be 140 µg/kg given on a schedule of every other day for 3 doses every 3 weeks. Although less immunogenic than the first-generation antimesothelin immunotoxin SS1P, the majority of patients developed antidrug antibodies after 2 cycles, indicating that LMB-100 has limited antitumor efficacy as a single agent. Phase 2 studies of LMB-100 plus pembrolizumab currently are ongoing for patients with mesothelioma and lung cancer."

Clinical • Journal • P1 data • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

A Differential Proteomic Approach to Characterize the Cell Wall Adaptive Response to CO Overpressure during Sparkling Wine-Making Process. (PubMed, Microorganisms) - "Over-represented proteins under pressure were involved in cell wall integrity (Ecm33p and Pst1p), protein folding (Ssa1p and Ssa2p), and glucan remodeling (Exg2p and Scw4p)...The use of flor yeasts for sparkling wine elaboration and improvement is proposed. Further research based on the genetic engineering of wine yeast using those genes from protein biomarkers under pressure alongside the second fermentation in bottle is required to achieve improvements."

Journal

Immunotoxin SS1P is rapidly removed by proximal tubule cells of kidney, whose damage contributes to albumin loss in urine. (PubMed, Proc Natl Acad Sci U S A) - "SS1P uptake by kidney is reduced by coadministration of l-lysine. Our data suggests that l-lysine administration to humans might prevent SS1P-mediated kidney damage, reduce albumin loss in urine, and alleviate capillary leak syndrome."

Journal • Oncology • Renal Disease

Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors. (PubMed, Biomolecules) - "This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox's. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents."

Journal • Review • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Thoracic Cancer • MSLN

Brettanomyces bruxellensis SSU1 haplotypes confer different sulfite tolerance when expressed in a Saccharomyces cerevisiae SSU1 null mutant. (PubMed, Appl Environ Microbiol) - "Generally, this strategy does not interfere with primary alcoholic fermentation, as wine strains of Saccharomyces cerevisiae exhibit significant SO tolerance, largely driven by the efflux pump Ssu1p...Gene expression analysis showed greater expression of the haplotype conferring greater SO tolerance. Our results suggest that a combination of BbSSU1 haplotype efficiency, copy number and haplotype expression levels likely contribute to the diverse SO tolerances observed for different B. bruxellensis strains."

Journal

SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma (clinicaltrials.gov) - P1/2; N=55; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting ➔ Completed

Clinical • Trial completion