Control of Metastases via Myeloid CD39 and NK Cell Effector Function.

Natural killer (NK) cell protection from tumor metastases is a critical feature of the host immune response to cancer, but various immunosuppression mechanisms limit NK cell effector function. The ectoenzyme, CD39, expressed on tumor-infiltrating myeloid cells, granulocytes, and lymphocytes, including NK cells, converts extracellular ATP (eATP) into AMP and, thus, potentially suppresses eATP-mediated proinflammatory responses. A CD39-targeting monoclonal antibody (mAb) that inhibits the mouse ectoenzyme CD39 suppressed experimental and spontaneous metastases in a number of different tumor models and displayed superior antimetastatic activity compared with the CD39 inhibitor POM1 and inhibitors and mAbs that block other members of the adenosinergic family (e.

Dual targeting of RANKL and PD-1 with a bispecific antibody improves anti-tumor immunity.

Objectives: The addition of RANKL/RANK blockade to immune checkpoint inhibitors (ICIs) such as anti-PD-1/PD-L1 and anti-CTLA4 antibodies is associated with increased anti-tumor immunity in mice. Recent retrospective clinical studies in patients with advanced melanoma and lung cancer suggest the addition of anti-RANKL antibody to ICI increases the overall response rate relative to ICI treatment alone. Based on this rationale, we developed a novel bispecific antibody (BsAb) co-targeting RANKL and PD-1.

CD96 targeted antibodies need not block CD96-CD155 interactions to promote NK cell anti-metastatic activity.

CD96 is a transmembrane glycoprotein Ig superfamily receptor, expressed on various T cell subsets and NK cells, that interacts with nectin and nectin-like proteins, including CD155/polio virus receptor (PVR). Here, we have compared three rat anti-mouse CD96 mAbs, including two that block CD96-CD155 (3.3 and 6A6) and one that does not block CD96-CD155 (8B10).

Scalable Manufacturing of Solderable and Stretchable Physiologic Sensing Systems.

Methods for microfabrication of solderable and stretchable sensing systems (S4s) and a scaled production of adhesive-integrated active S4s for health monitoring are presented. S4s' excellent solderability is achieved by the sputter-deposited nickel-vanadium and gold pad metal layers and copper interconnection. The donor substrate, which is modified with "PI islands" to become selectively adhesive for the S4s, allows the heterogeneous devices to be integrated with large-area adhesives for packaging.