An Immunomodulator-Boosted Lactococcus Lactis Platform For Enhanced In Situ Tumor Vaccine.

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.

Acidity-targeting transition-aided universal chimeric antigen receptor T-cell (ATT-CAR-T) therapy for the treatment of solid tumors.

The use of CAR-T cells in treating solid tumors frequently faces significant challenges, mainly due to the heterogeneity of tumor antigens. This study assessed the efficacy of an acidity-targeting transition-aided universal chimeric antigen receptor T (ATT-CAR-T) cell strategy, which is facilitated by an acidity-targeted transition. Specifically, the EGFRvIII peptide was attached to the N-terminus of a pH-low insertion peptide. Triggered by the acidic conditions of the tumor microenvironment, this peptide alters its structure and selectively integrates into the membrane of solid tumor cells. The acidity-targeted transition component effectively relocated the EGFRvIII peptide across various tumor cell membranes; thus, allowing the direct destruction of these cells by EGFRvIII-specific CAR-T cells. This method was efficient even when endogenous antigens were absent. In vivo tests showed marked antigen modification within the acidic tumor microenvironment using this component. Integrating this component with CAR-T cell therapy showed high effectiveness in combating solid tumors. These results highlight the capability of ATT-CAR-T cell therapy to address the challenges presented by tumor heterogeneity and expand the utility of CAR-T cell therapy in the treatment of solid tumors.

Establishment of the fingerprint of Temurin- 5 powder and content determination of 4 components / 中国药房

OBJECTIVE To establish the fing erprint of Temurin- 5 powder，conduct chemical pattern recognition analysis ，and determine the contents of 4 components simultaneously. METHODS The fingerprints of 10 batches of Temurin- 5 powder were established and similarity evaluation was performed by using high performance liquid chromatography （HPLC）combined with the Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）；common peaks were identified by comparing with mixed substance control. The common peaks were analyzed by systematic cluster analysis and principal component analysis with SPSS 26.0 software. The HPLC method was used to determine the contents of gallic acid ， geniposide，chlorogenic acid and ellagic acid in 10 batches of samples. RESULTS A total of 15 common peaks were identified from the fingerprints of 10 batches of Temurin-5 powder，and the similarity was 0.997-0.999. It was identified that peak 1 was gallic acid ，peak 3 was geniposide ，peak 5 was chlorogenic acid and peak 12 was ellagic acid. Among the 10 batches of samples ， S4 and S 9 were grouped into one category ，S6-S8 were grouped into one category ，and the other batches of samples were grouped into one category. The accumulative variance contribution rate of first three principal components was 89.245％. The linear ranges of gallic acid ，geniposide，chlorogenic acid and ellagic acid were 5.55-177.5，15.98-511.5，2.56-82.0 and 13.48-431.5 μg/mL， respectively. RSDs of precision ，stability（24 h）and repeatability tests were all less than 2％（n＝6 or n＝7）. The average recoveries were 101.56％，102.21％，98.60％ and 96.62％，respectively，RSDs were 1.90％，1.61％，1.58％ and 1.73％（n＝6）. Average contents of above components were 5.03-5.64，10.38-12.16，1.40-1.69，6.47-7.11 mg/g，respectively. CONCLUSIONS The established fingerprint is stable and feasible ，and the content determination method meets the relevant regulations. Combined with chemical pattern recognition analysis ，it can be used for the quality control of Temurin- 5 powder.