Genetic dissection of bull fertility in US Jersey dairy cattle.

The service sire has been recognized as an important factor affecting herd fertility in dairy cattle. Recent studies suggest that genetic factors explain part of the difference in fertility among Holstein sires. The main objective of this study was to dissect the genetic architecture of sire fertility in US Jersey cattle.

Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial.

Importance: Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity.

Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy.

TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells.

Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN.

As Toll-like receptors (TLR) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy of therapies for squamous cell carcinoma of the head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes. A phase Ib clinical trial assessed the safety and antitumor activity of motolimod in combination with cetuximab in patients with SCCHN.

Motolimod effectively drives immune activation in advanced cancer patients.

A novel approach to immunotherapy is the activation of toll-like receptor 8 (TLR8). Motolimod, a selective TLR8 agonist can act in concert with approved immunotherapies to sensitize T cells and augment natural killer (NK) cell function. Despite treatment with chemotherapeutic agents and advance disease, cancer patients remain sensitive to motolimod.