Rabbit Anti-Human EGF Polyclonal Antibody

Immune selection drives tumor cells to acquire refractory phenotypes. We previously demonstrated that cytotoxic T lymphocyte (CTL)-mediated immune pressure enriches NANOG(+)tumor cells with stem-like and immune-refractory properties that make them resistant to CTLs. Here, we report that the emergence of refractory phenotypes is highly associated with an aberrant macroautophagic/autophagic state of the NANOG(+)tumor cells and that the autophagic phenotype arises through transcriptional induction ofMAP1LC3B/LC3Bby NANOG. Furthermore, we found that upregulation of LC3B expression contributes to an increase in EGF secretion. The subsequent hyperactivation of EGFR-AKT signaling rendered NANOG(+)tumor cells resistant to CTL killing. The NANOG-LC3B-p-EGFR axis was preserved across various types of human cancer and correlated negatively with the overall survival of cervical cancer patients. Inhibition of LC3B in immune-refractory tumor models rendered tumors susceptible to adoptive T-cell transfer, as well as PDCD1/PD-1 blockade, and led to successful, long-term control of the disease. Thus, our findings demonstrate a novel link among immune-resistance, stem-like phenotypes, and LC3B-mediated autophagic secretion in immune-refractory tumor cells, and implicate the LC3B-p-EGFR axis as a central molecular target for controlling NANOG(+)immune-refractory cancer.

Bone-marrow-derived mesenchymal stem cells (MSCs) are of growing interest for the treatment of diabetic wound healing. However, they are often associated with poor proliferation and viability at the wounded site. Here, it is reported the use of human epidermal growth factor -curcumin bandage bioconjugate (EGF-Cur B) loaded with MSCs (MSCs-EGF-Cur B) at the wounded site for diabetic wound healing. Conjugation efficiency of EGF was determined by FTIR and XPS, surface morphology was analyzed by SEM and AFM and hydrophilicity by contact angle. Chemical integrity of curcumin with the polymeric matrix was studied by FTIR and, antiinflamatory and biocompatibility of EGF-Cur B were determined by TNF alpha ELISA and MTT study respectively. The culture of MSCs over EGF-Cur B enhanced MSC viability and expression of transcription factors associated with the maintenance of pluripotency and self-renewal (OCT3/4, SOX2, and Nanog) as compared to MSCs grown in standard conditions. Its therapeutic effect was examined on diabetic full-thickness excisional wound model in terms of size and histological examination. Synergetic combinational approach especially when treated with MSCs-EGF-Cur B significantly enhanced wound closure by increasing granulation tissue formation, collagen deposition, and angiogenesis as compared to other groups. In conclusion, biocompatible therapeutic MSCs-EGF-Cur B might have great application for diabetic wound healing in the near future.