While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies.
With the rapid progression of additive manufacturing and the emergence of new 3D printing technologies, accuracy assessment is mostly being performed on isosymmetric-shaped test bodies. However, the accuracy of anatomic models can vary. The dimensional accuracy of root mean square values in terms of trueness and precision of 50 mandibular replicas, printed with five common printing technologies, were evaluated. The highest trueness was found for the selective laser sintering printer (0.11 ± 0.016 mm), followed by a binder jetting printer (0.14 ± 0.02 mm), and a fused filament fabrication printer (0.16 ± 0.009 mm). However, highest precision was identified for the fused filament fabrication printer (0.05 ± 0.005 mm) whereas other printers had marginally lower values. Despite the statistically significance (p < 0.001), these differences can be considered clinically insignificant. These findings demonstrate that all 3D printing technologies create models with satisfactory dimensional accuracy for surgical use. Since satisfactory results in terms of accuracy can be reached with most technologies, the choice should be more strongly based on the printing materials, the intended use, and the overall budget. The simplest printing technology (fused filament fabrication) always scored high and thus is a reliable choice for most purposes. therefore apply to different fields of medicine and dentistry. With the continuous development of each individual technology, none stand out significantly from the others and so all are represented in the daily medical routine.Even though AM was introduced into medicine many years ago, the production of anatomical models often is still one of the main areas of application [3][4][5][6]. In opinion polls, surgeons still tend to regard anatomical models as advantageous for daily work [7]. For instance, anatomical models offer numerous advantages over other learning resources in understanding complex anatomical correlations [8]. The combination of optical and tactile sensitivity leads to a superior understanding and has defined the concept "touch to comprehend" [9]. A meta-analysis of 158 studies from 2005 to 2015 described further advantages such as possibilities for preoperative planning and time savings in the operating room, but emphasized that accuracy was not satisfactory in 34 studies [10]. Although most manufacturers provide the specifications in terms of accuracy, these are mostly uncertain in the final clinical application. In addition, most tests are performed on isosymmetric-shaped bodies [11], but the use of anatomical models may reveal larger dimensional errors. Measurements with skull and mandibular models revealed incorrect or completely missing anatomy [12]. Even deformations of 3D printed dental surgical guides were reported [13]. Inaccuracies in 3D printing applications can lead to inappropriate treatment that could harm the patient.Identical procedures with the same material under the same circumstances do not necessary lead to identical results. Statistical standards descr...
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