This paper presents a new approach for an online solution of the inverse kinematics problem based on nonlinear optimization for robots with joint physical constraints. The inverse kinematics problem is stated as a constrained nonlinear optimization problem and is solved using Kuhn-Tucker conditions analysis. The nonlinear multivariable optimization problem is locally converted into independent local linear constrained subproblems and each subproblem is analytically solved. For each joint, position limits and velocity limits are considered as physical constraints. The proposed structure benefits from a very low complexity design. The proposed method is fast and requires few calculations. The convergence of the proposed algorithm is proven based on the Lyapunov function. While keeping the algorithm stable, it can navigate the manipulator to a desired position under joint physical limits. The algorithm is simulated on a 7-DOF PA-10 manipulator. Results indicate good efficiency for the proposed structure in constrained path planning of joint space.
Cell therapy is an innovative approach that permits numerous possibilities in the field of cancer treatment. CAR-T cells have been successfully used in hematologic relapsed/refractory patients. However, the need for autologous sources for T cells is still a major drawback. CAR-NK cells have emerged as a promising resource using allogeneic cells that could be established as an off-the-shelf treatment. NK cells can be obtained from various sources, such as peripheral blood (PB), bone marrow, umbilical cord blood (CB), and induced pluripotent stem cells (iPSC), as well as cell lines. Genetic engineering of NK cells to express different CAR constructs for hematological cancers and solid tumors has shown promising preclinical results and they are currently being explored in multiple clinical trials. Several strategies have been employed to improve CAR-NK cell expansion and cytotoxicity efficiency. In this article, we review the latest achievements and progress made in the field of CAR-NK cell therapy.
Background
Targeting of specific tissues and cells by viruses is one of the challenges faced by researchers. Lentiviral vectors (LVs) are one of the most promising gene delivery systems in cancer gene therapy. Therefore, we aimed to design a novel lentiviral delivery system that expresses anti‐ human epidermal growth factor 2 (HER2) designed anykrin repeat protein (DARPin) on the vector envelope to create a pseudotyped lentivirus for targeting HER2‐positive cancer cells.
Methods
A helper plasmid producing the viral vector envelope containing anti‐HER2 DARPin‐G3 was constructed. LV was produced by transfer vector containing green fluorescent protein (GFP) gene and helper plasmids in human embryonic kidney 293 cells. The human breast cancer cell lines SKBR3 (normal and with inhibited endocytosis) (HER2‐positive) and MDA‐MB‐231 (HER2‐negative) were transduced by the recombinant viral vector. The GFP‐based transduction rate was determined by flow cytometry and fluorescence microscopy.
Results
The anti‐HER2 DARPin concentration in DARPin‐LVs was significantly higher than the envelope G glycoprotein of the vesicular stomatitis virus‐LVs (non‐anti‐HER2 control) (p < 0.0001). In flow cytometry assays, the percentage of transduction by recombinant LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0074) and MDA‐MB‐231 cells (p = 0.0037). In fluorescence microscopy assays, the percentage of transduction by new LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0026) and MDA‐MB‐231 cells (p = 0.0014).
Conclusions
We constructed a new recombinant LV with a defect in cell entry directly, containing an anti‐HER2 DARPin on the vector envelope with specific tropism to HER2 receptor on HER2‐positive cancer cells. We assumed that this viral vector transduces cells via an endocytosis‐dependent process.
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