Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

[Dynamics of habitat suitability for waterfowls from 1990 to 2015 in the ecological function zone of Sanjiang Plain, Northeast China]. / 1990­2015å¹´ä¸‰æ±Ÿå¹³åŽŸç”Ÿæ€åŠŸèƒ½åŒºæ°´ç¦½æ –æ¯åœ°é€‚å®œæ€§åŠ¨æ€.

As a wetland of international importance, the ecological function zone of the Sanjiang Plain (EFZSP) plays an important role in maintaining waterfowl habitat. With the increasing disturbance of human beings, land use and climate changes, habitat suitability for waterfowls (HSW) has drawn greater attention of ecologists. In this study, Landsat TM/ETM+/OLI and HJ-1B images in 1990, 2000, 2010 and 2015 were used to obtain land cover classification by object-based image analysis, and the entropy and analytic hierarchy process methods were adopted to determine the factors and their weights, the factors selected in this study included water condition (lake and river density), disturbance factor (residence and road density), shelter condition (land cover type and slope), and food abundance (NDVI). Finally, the evaluation results of habitat suitability of year 1990, 2000, 2010, and 2015 were achieved based on the habitat suitability index (HSI) system, and the spatio-temporal dynamics and driving forces causing the changes were analyzed. The results showed that the excellent level of HSW mainly distributed in abundant water areas, especially along the riparian zone of the Heilongjiang River, Naoli River, Ussuri River, Muling River and Xingkai Lake. Its area decreased by 3.2% from 1990 to 2015 because of wetland reclamation. The good level of HSW concentrated in Raohe County over the past 25 years, the condition of Hulin County and Fuyuan County were improved to a good level from 2010 to 2015 due to the substantial increase of paddy field areas. The fair level of HSW distributed dispersedly, and the areas first increased from 1990 to 2000 and then decreased during 2000-2010 and 2010-2015 periods. The areas of poor le-vel increased by 6.7% from 1990 to 2000 and decreased by 3.1% from 2000 to 2015. The change of HSW level in this study area was dominated by land cover change, and both of the increasing population and economy and the drying and worming climate resulted in the decline of the HSW level, whereas the establishment of nature reserves is crucial to protect habitat for waterfowls.

Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma.

Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).

[Wetlands of priority restoration in Northeast China based on spatial analysis].

By using GIS/RS technology, and from the aspects of landscape structure, river- and road densities, wetness index, geomorphology, and cultivated land productivity, a spatial analysis was made on the potentiality of wetland restoration in Northeast China, with the regions of priority and secondary priority restoration wetlands determined. Then, by using the coordinated development index of crop production and wetland as well as the landscape indices, the wetland restoration effect was verified. In Northeast China, the wetland area of priority restoration was 1.78 x 10(6) hm2, among which, farmland and grassland were the main types for restoration, accounting for 96.7% of the total, and mainly located in the Sanjiang Plain in the northeastern part and the Songnen Plain in the central part of Northeast China. The wetland area of secondary priority restoration was 1.03 x 10(6) hm2. After the restoration of the wetlands, the wetland area in Northeast China would be increased by 37.4%, compared with the present wetland area, and the value of the coordinated development index of crop production and wetland would increase from 0.539 before restoration to 0.733 after restoration. The landscape pattern would be more benefit to the performance of the ecological functions of the wetlands. This study revealed that the restoration scheme of the wetlands in Northeast China based on spatial analysis was practicable, which could provide data support for the implement of wetland restoration and the improvement of ecological environment in Northeast China.

[T cell receptor diversity of CD8+ T lymphocytes and its association with viral load in individuals with HIV-1 infection].

OBJECTIVE: To determine the complementary determining region 3 (CDR3) length diversity of T cell receptor Vbeta repertoires of CD8+ T lymphocytes and to explore its association with viral load in individuals with HIV-1 infection. METHODS: Separation of CD8+ T cells from peripheral blood mononuclear cells (PBMCs) was carried out by using immunomagnetic beads coated with anti-CD8 antibody. Total RNAs from the purified CD8+ T lymphocytes were isolated and used to perform polymerase chain reaction (PCR) amplifications in CDR3 of 22 T cell receptor (TCR) gene families. CDR3 diversity and its association with viral load in individuals with HIV-1 infection were analyzed. RESULTS: An average diversity for all CDR3 profiles in CD8+ T cells from 9 HIV-infected individuals was significantly different as compared to 7 age-matched healthy donors (P<0.05) with the HIV-infected individuals losing diversity in the CDR3 profiles. There was positive correlation between changes in TCR CDR3 diversity and viral load (r=0.771, P<0.05). The changes in CDR3 length diversity of Vbeta families in HIV-infected individuals, particular in Vbeta2, Vbeta4, Vbeta5, Vbeta17, Vbeta20, Vbeta21, Vbeta23, Vbeta24, were statistically different from the healthy controls. CONCLUSION: HIV-1 infection might induce the loss of TCR Vbeta repertoire diversity and disrupt the CDR3 distributions within CD8+ T cells. There should be positive correlation between changes in TCR CDR3 diversity and the viral load in HIV-1 infected patients.

CTL responses to regulatory proteins Tat and Rev in HIV-1 B'/C virus-infected individuals.

OBJECTIVE: To characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals. METHODS: HIV-1-specific CTL responses were analyzed by IFN-gamma ELISPOT assay using overlapping peptides spanning the consensus sequences of HIV-1 clade C Tat and Rev proteins. Statistical analysis and graphical presentation were performed using SIGMAPLOT 10.0 and SIGMASTAT 3.5. For samples with a positive response, the magnitude of CTL responses was compared between HIV-1 C proteins by Wilcoxon rank sum test, and the significance threshold was P<0.05. RESULTS: Tat and Rev were frequently recognized, with 23% and 52% of the tested individuals having detectable responses to these proteins, respectively. Several immunodominant regions were detected in Rev. No significant correlation was observed between the magnitude and breadth of CTL responses to regulatory proteins and the control of virus replication in this study. CONCLUSION: Tat and Rev can serve as targets for HIV-1-specific CTL, and several immunodominant regions are detectable in Rev. Further characterization of epitopes and their role in virus control may shed light on pathogenesis of HIV-1 natural infection and also be useful for the design and testing of candidate vaccines.