T-Cell Receptor Therapy in the Treatment of Ovarian Cancer: A Mini Review.

Ovarian cancer, in particularly high-grade serous ovarian cancer (HGSOC) and ovarian carcinosarcoma (OCS), are highly aggressive and deadly female cancers with limited treatment options. These tumors are generally unresponsive to immune check-point inhibitor (ICI) therapy and are referred to as immunologically "cold" tumors. Cell-based therapy, in particular, adoptive T-cell therapy, is an alternative immunotherapy option that has shown great potential, especially chimeric antigen receptor T cell (CAR-T) therapy in the treatment of hematologic malignancies. However, the efficacy of CAR-T therapy in solid tumors has been modest. This review explores the potential of another cell-based therapy, T-cell receptor therapy (TCR-T) as an alternate treatment option for immunological "cold" OC and OCS tumors.

Global Variation in Use of Enteral Nutrition for Pediatric Crohn Disease.

OBJECTIVES: Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center-based variation in use and diversity in practice, we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy. METHODS: This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Pediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the Pediatric Gastrointestinal-Bulletin Board (PEDGI-BB). Data were collected into REDCap and analyzed using descriptive statistics. RESULTS: In total, 146 participants from 26 countries completed the survey. Sixty-five percentage of participants were general, non-inflammatory bowel diseases (IBD)-focused pediatric gastroenterologists, 21% were IBD-focused, and 10% were dietitians. The most common indications (∼90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial enteral nutrition (EN) after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage. CONCLUSIONS: We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing.

Fibrillar oligomers nucleate the oligomerization of monomeric amyloid beta but do not seed fibril formation.

Soluble amyloid oligomers are potent neurotoxins that are involved in a wide range of human degenerative diseases, including Alzheimer disease. In Alzheimer disease, amyloid beta (Abeta) oligomers bind to neuronal synapses, inhibit long term potentiation, and induce cell death. Recent evidence indicates that several immunologically distinct structural variants exist as follows: prefibrillar oligomers (PFOs), fibrillar oligomers (FOs), and annular protofibrils. Despite widespread interest, amyloid oligomers are poorly characterized in terms of structural differences and pathological significance. FOs are immunologically related to fibrils because they react with OC, a conformation-dependent, fibril-specific antibody and do not react with antibodies specific for other types of oligomers. However, fibrillar oligomers are much smaller than fibrils. FOs are soluble at 100,000 x g, rich in beta-sheet structures, but yet bind weakly to thioflavin T. EPR spectroscopy indicates that FOs display significantly more spin-spin interaction at multiple labeled sites than PFOs and are more structurally similar to fibrils. Atomic force microscopy indicates that FOs are approximately one-half to one-third the height of mature fibrils. We found that Abeta FOs do not seed the formation of thioflavin T-positive fibrils from Abeta monomers but instead seed the formation of FOs from Abeta monomers that are positive for the OC anti-fibril antibody. These results indicate that the lattice of FOs is distinct from the fibril lattice even though the polypeptide chains are organized in an immunologically identical conformation. The FOs resulting from seeded reactions have the same dimensions and morphology as the initial seeds, suggesting that the seeds replicate by growing to a limiting size and then splitting, indicating that their lattice is less stable than fibrils. We suggest that FOs may represent small pieces of single fibril protofilament and that the addition of monomers to the ends of FOs is kinetically more favorable than the assembly of the oligomers into fibrils via sheet stacking interaction. These studies provide novel structural insight into the relationship between fibrils and FOs and suggest that the increased toxicity of FOs may be due to their ability to replicate and the exposure of hydrophobic sheet surfaces that are otherwise obscured by sheet-sheet interactions between protofilaments in a fibril.