Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy

Metastatic bone and soft tissue sarcomas often relapse after chemotherapy (CHT) and molecular targeted therapy (mTT), maintaining a severe prognosis. A subset of sarcoma cancer stem cells (sCSC) is hypothesized to resist conventional drugs and sustain disease relapses. We investigated the immunotherapy activity of cytokine induced killer cells (CIK) against autologous sCSC that survived CHT and mTT. The experimental platform included two aggressive bone and soft tissue sarcoma models: osteosarcoma (OS) and undifferentiated-pleomorphic sarcoma (UPS). To visualize putative sCSC we engineered patient-derived sarcoma cultures (2 OS and 3 UPS) with a lentiviral sCSC-detector wherein the promoter of stem-gene Oct4 controls the expression of eGFP. We visualized a fraction of sCSC (mean 24.2 +/- 5.2%) and confirmed their tumorigenicity in vivo. sCSC resulted relatively resistant to both CHT and mTT in vitro. Therapeutic doses of doxorubicin significantly enriched viable eGFP(+)sCSC in both OS (2.6 fold, n = 16) and UPS (2.3 fold, n = 29) compared to untreated controls. Treatment with sorafenib (for OS) and pazopanib (for UPS) also determined enrichment (1.3 fold) of viable eGFP(+)sCSC, even if less intense than what observed after CHT. Sarcoma cells surviving CHT and mTT were efficiently killed in vitro by autologous CIK even at minimal effector/target ratios (40:1 = 82%, 1:4 = 29%, n = 13). CIK immunotherapy did not spare sCSC that were killed as efficiently as whole sarcoma cell population. The relative chemo-resistance of sCSC and sensitivity to CIK immunotherapy was confirmed in vivo. Our findings support CIK as an innovative, clinically explorable, approach to eradicate chemo-resistant sCSC implicated in tumor relapse

MXene materials based printed flexible devices for healthcare, biomedical and energy storage applications

The advent of cost effective printed smart devices has revolutionized the healthcare sector by allowing disease prediction and timely treatment through non-invasive real time and continuous health monitoring. Future advancements in printed electronic (PE) materials will continue to enhance the quality of human living. For any PE application, materials should possess proper mechanical integrity and resistivity while being non-toxic. In the case of sensing devices for physiological and biochemical signals, excellent conductivity is an essential requirement for obtaining high response signals. The emergence of the novel class of 2D materials called MXenes and their composites has resulted in structures and materials hugely relevant for healthcare devices. Exploiting solution based 2D MXene materials can expedite their practical application in PE devices by overcoming the present limitations of conductive inks such as poor conductivity and the high cost of alternative functional inks. There has been much progress in the MXene functional ink generation and its PE device applications since its discovery in 2011. This review summarizes the MXene ink formulation for additive patterning and the development of PE devices enabled by them in healthcare, biomedical and related power provision applications