preparation-characteristics-toxicity-efficacy-evaluation-nasal-self

Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-Assembled Nanoemulsion Tumor Vaccine <em>In Vitro</em> and <em>In Vivo</em>

Epitope peptides have attracted widespread attention in the field of tumor vaccines because of their safety, high specificity, and convenient production; ...

Third Military Medical University of Chinese PLA

This study aimed to improve the solubility, reduce the side effects and enhance the efficacy of gambogic acid against acute myeloid leukemia in vitro and in vivo. This oil-in-water nanoemulsion (average size 17.20 ± 0.11 nm, zeta potential 4.17 ± 0.82 mV) containing Tween-80, glycol, squalene and gambogic acid with improving 4000 times solubility was prepared by pseudoternary phase diagrams. We found that this nanoemulsion successfully encapsulated gambogic acid; it was stable and showed an obvious delayed release effect for the drug in three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half inhibiting concentration (IC) of this nanoemulsion (480.7 μg/mL and 408 μg/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 μg/mL and 206 μg/mL) after acting on the toxicity standard cell line (L929 line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity indicated that the half lethal dose (LD) of this nanoemulsion (23.25 mg/kg, 95% LD, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD, 16.84-20.53 mg/kg). Compared with its suspension, the bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion had a better efficacy against the acute myeloid leukemia in vitro and in vivo by improving the time and percent of survival (MV4-11 engrafts mice) and reducing half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL-60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a promising therapeutic medicine for acute myeloid leukemia.

Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo.

CD3CD20 T cells are a population of CD3 T cells co-expressing CD20 that make up to ∼3-5% of the CD3 T-cell compartment in the peripheral blood of human beings. In healthy individuals, CD3CD20 T cells are heterogeneous for containing a lower proportion of CD4 cells, but produce higher levels of IL-17A and/or IFN-γ than those of CD3CD20 T cells. Recently, emerging studies have shown a pathogenic behavior of CD3CD20 T cells in autoimmune diseases and CD20 T-cell malignancies, and patients with the diseases may benefit from anti-CD20 immunotherapy to deplete these cells. However, CD3CD20 T cells may also play a protective role in ovarian cancer and HIV infection for their strong propensity to IFN-γ production. In this review, we will describe the current knowledge about CD3CD20 T-cell biology, and discuss their functional roles in autoimmune diseases as well as cancer and infectious diseases.

CD3CD20 T cells and their roles in human diseases.

Overexpression of programmed cell death protein 1 (PD-1) is linked to CD8+ T cell dysfunction and contributes to tumor immune escape. However, the prevalence and functional regulations of PD-1 expression on CD8+ T cells in human gastric cancer (GC) remain largely unknown.

PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer.

CD8CD103 tissue-resident memory T cells (TRMs) are involved in tumor immune response and linked to favorable clinical outcome in human cancer. However, the distribution, phenotype, functional properties and clinical relevance of these cells in gastric cancer (GC) remain elusive. Here, our data show that, in comparison to non-tumor tissues, the percentages of CD8CD103 TRMs in tumors are significantly decreased. Most tumor-infiltrating CD8CD103 TRMs are CD45RACCR7 effector-memory cells with higher PD-1 and 4-1BB expression than those from non-tumor tissues. Further, tumor-infiltrating CD8CD103 TRMs show impaired cytolytic capacity due to decreased granzyme B and perforin expression. Moreover, ex vivo PD-1 blockade could restore the cytolytic capacity of tumor-infiltrating CD8CD103 TRMs, and such anti-PD-1-mediated reinvigoration of CD8CD103 TRMs could be further enhanced by 4-1BB co-stimulation. Finally, lower levels of Tumor-infiltrating CD8CD103 TRMs are positively correlated with GC progression and poor patients' survival. Our data suggest that restoring CD8CD103 TRM function by combining PD-1 blockade and 4-1BB co-stimulation may be a promising strategy for treating GC.

Article	Year
Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences\| PubMed ID: 30296572	2018
CD3CD20 T cells and their roles in human diseases. Human immunology\| PubMed ID: 30639700	2019
PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer. Journal for immunotherapy of cancer\| PubMed ID: 32753468	2020
Distribution, phenotype, functional and clinical relevance of CD8CD103 tissue-resident memory T cells in human gastric cancer. Cancer immunology, immunotherapy : CII\| PubMed ID: 34767045	2022

Liusheng Peng

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