Enhanced presentation of MHC class Ia, Ib and class II-restricted peptides encapsulated in biodegradable nanoparticles: a promising strategy for tumor immunotherapy

<p>Abstract</p> <p>Background</p> <p>Many peptide-based cancer vaccines have been tested in clinical trials with a limited success, mostly due to difficulties associated with peptide stability and delivery, resulting in inefficient antigen presentation. Therefore, the development of suitable and efficient vaccine carrier systems remains a major challenge.</p> <p>Methods</p> <p>To address this issue, we have engineered polylactic-co-glycolic acid (PLGA) nanoparticles incorporating: (i) two MHC class I-restricted clinically-relevant peptides, (ii) a MHC class II-binding peptide, and (iii) a non-classical MHC class I-binding peptide. We formulated the nanoparticles utilizing a double emulsion-solvent evaporation technique and characterized their surface morphology, size, zeta potential and peptide content. We also loaded human and murine dendritic cells (DC) with the peptide-containing nanoparticles and determined their ability to present the encapsulated peptide antigens and to induce tumor-specific cytotoxic T lymphocytes (CTL) <it>in vitro</it>.</p> <p>Results</p> <p>We confirmed that the nanoparticles are not toxic to either mouse or human dendritic cells, and do not have any effect on the DC maturation. We also demonstrated a significantly enhanced presentation of the encapsulated peptides upon internalization of the nanoparticles by DC, and confirmed that the improved peptide presentation is actually associated with more efficient generation of peptide-specific CTL and T helper cell responses.</p> <p>Conclusion</p> <p>Encapsulating antigens in PLGA nanoparticles offers unique advantages such as higher efficiency of antigen loading, prolonged presentation of the antigens, prevention of peptide degradation, specific targeting of antigens to antigen presenting cells, improved shelf life of the antigens, and easy scale up for pharmaceutical production. Therefore, these findings are highly significant to the development of synthetic vaccines, and the induction of CTL for adoptive immunotherapy.</p

Navigation Improves the Survival Rate of Mobile-Bearing Total Knee Arthroplasty by Severe Preoperative Coronal Deformity: A Propensity Matched Case-Control Comparative Study.

The primary hypothesis of this study was that the survival rate over 10 years of total knee arthroplasties (TKAs) implanted with a navigation system was superior to that of TKAs implanted with a conventional technique. The secondary hypothesis was that the severity of the initial coronal deformity had a negative influence on the survival rate. A national, multicentric, retrospective study was performed in France, including eight university or private centers with high volumes in knee surgery. Cases operated on with either a conventional (control group) or a navigated (study group) technique were matched after calculating the propensity score using the logistic regression technique. All patients were contacted after 10 years or more to determine the survival of the TKA. The need for date and cause of revision were noted. The primary end point of the study was the occurrence of a revision for any mechanical reason. Survival curves were calculated using the Kaplan-Meier's technique, with the primary criterion as end point. The influence of the implantation technique was analyzed by a log-rank test at a 5% level of significance. The influence of severity of the preoperative coronal deformity was analyzed using the same technique. A total of 513 cases were included in each group. The survival rates after 13 years were 96.5% in the study group and 92.9% in the control group (not significant). There was no significant difference between both groups for the survival rates after 13 years for small deformity (96.0 vs. 97.0%), but the difference was significant for large deformity (97.0 vs. 89.0%, p = 0.04). The results suggest that the use of a navigation system, allowing a more consistent correction of the preoperative coronal deformity, thus allows a better long-term prosthetic survival in cases with a large initial coronal deformity. A navigation system should be routinely used in cases of initial coronal deformity greater than or equal to 10 degrees, as conventional techniques do not routinely provide satisfactory axial correction in these difficult cases

No difference in 13-year survival after medial pivot or central pivot mobile bearing total knee arthroplasty. A propensity matched comparative analysis.

The present study was designed to evaluate the long-term results (more than 10 years) of mobile bearing total knee arthroplasty (TKA) and to compare the survival of medial pivot axis (MPA) and central pivot axis (CPA) TKAs. The primary hypothesis was that the 10- to 15-year survival rate of MPA TKAs will be better than CPA TKAs. A national, multicenter, retrospective study was performed in France. In this case-control design, 1154 TKAs were paired into the CPA group (control group: 577 cases) and MPA group (study group: 577 cases) based on a logistic regression analysis of age, gender, body mass index and severity of the coronal deformity, defining the propensity score for each case. Final survival information follow-up was obtained for 946 cases (82%). There was no significant difference between the control and study groups for any baseline data. Twenty-two prosthetic revisions (2%) were performed for mechanical reasons during the follow-up period. There was no significant difference between the 13-year survival rates of CPA (98%) and MPA (97%) TKAs. There was no significant difference between groups in their final Oxford and Knee Society scores. Our findings do not support the assumption that medialization of the pivot axis of a mobile bearing TKA improves clinical results or survival. Level III

Influence of preoperative factors on the gain in flexion after total knee arthroplasty

International audienceFinal flexion mobility after a total knee arthroplasty is an important factor in patient comfort. Some patients gain in flexion mobility, others do not. Is it possible to identify the clinical factors related to the patient that predicted the final gain in flexion? Materials and methods: A multicenter retrospective study directed by the Societe francaise de la hanche etdu genou (SFHG) was conducted on 1601 cases of total knee arthroplasty that had presented no complications and a minimal follow-up of 2 years. The gain in flexion was assessed by the difference between the preoperative and the final range of flexion. The range of the gain in flexion was tested based on eight factors: age, gender, etiology, body mass index, frontal deformity, preoperative flexum deformity and four levels of preoperative mobility: = 130 degrees. Results: A mean gain in flexion of 8.4 degrees +/- 14 degrees was found for the overall series. In 66% of cases, we found an increase of flexion and in 19% a loss of flexion. In cases with BMI higher than 35, varus deformity with an HKA angle = 130 degrees'' group. A decrease in flexion was noted in 51% of the cases in the latter group. Other factors such as age, sex, and etiology had no influence on the gain in flexion. Discussion: After TKA, a gain in flexion was often noted. The amount of gain depended on the preoperative range of flexion: the lower this level was, the more flexion increased. The presence of a varus deformity, morbid obesity, or flessum was associated with greater gain in flexion, even if the final flexion was lower than the mean flexion in the overall population. The search for these factors made it possible to predict a gain in flexion and discuss this with the patient. (C) 2015 Elsevier Masson SAS. All rights reserved

Inconsistent relationship between body weight/body mass index prior to total knee arthroplasty and the 12-year survival

Background: The primary hypothesis was that body weight (BW) and body mass index (BMI) significantly impact the long-term survival rate after implantation of a mobile bearing total knee arthroplasty (TKA).Methods: A national, multicentric, retrospective study was performed in France. A total of 1604 TKAs were included. The 10-year follow-up was documented, and the influence of BW and BMI on the survival rate was assessed.Results: There was a significant influence of the BW on the 12-year survival rate for any reason and for infection; but this influence was not proportional to the BW or BM]. There was no significant influence of the BMI on the 12-year survival rate for any reason, for any mechanical reason or for infection.Conclusion: Our results suggest that a higher BMI should not be considered as a risk factor for revision for mechanical purpose if a mobile bearing TKA with confirming design is implanted. (C) 2019 Elsevier B.V. All rights reserved