AbbVie has recently licensed rights to a monoclonal antibody discovered by Argenx, ARGX-115, paying $20MM up-front and up to $625MM in milestones based on development, approval, and commercial performance. This monoclonal antibody targets a central player in the complex tumor microenvironment – the regulatory T-cell (Treg). Continue reading
Category Archives: Tumor Microenvironment
Mutational burden biomarker – not just mismatch repair deficiency
We have discussed mutational burden previously on this blog – in essence, the concept is that tumors with more mutations are more visible to the immune system because the generation of new novel antigenic epitopes allows for adaptive immune responses even when previous adaptive antigen-specific immune responses have been blunted by PD-1 expression. Continue reading
SEMA4D/CD100, a novel target for immune-oncology
Semaphorins are secreted, transmembrane, and glycosylphosphatidylinisotol-anchored glycoproteins that are important in cell to cell signaling. Humans have 20 semaphorins, the most of any species analyzed to date. Their role was originally identified in the development of the nervous system and axonal guidance. Since then, they have been shown to be important in the development and functioning of many tissues including: Continue reading
How important is inflammation in breast cancer progression?
Not very, according to the REACT Study conducted by the Imperial College London. The study was predicated on the importance of COX-2 in driving inflammation that contributes to tumorigenesis. The thinking was that administering celecoxib (Celebrex), a COX-2 inhibitor, could reduce breast cancer progression, as suggested in smaller observational trials. Continue reading
The levels of immune cells within ovarian cancer tumors correlate with survival
Researches with the Ovarian Tumor Tissue Analyses Consortium analyzed the CD8+ (cytotoxic T-cell) content of tumors from 5,500 patients and compared them with clinical outcome. The analysis was large enough to allow for comparison by histologic subtype – endometrioid, clear cell, mucinous, and low-grade serous ovarian cancer, as well as high-grade serous ovarian cancer. Included in the sample were 3,200 high grade serous ovarian cancers. Continue reading
Pancreatic cancer – early detection, immune response, and infection-based resistance
Approximately 1.6 percent of men and women will be diagnosed with pancreatic cancer at some point during their lifetime. In 2014, an estimated 64,668 patients were living with the disease. The five-year survival for pancreatic cancer is 8.2% and it is projected to be the second leading cause of death due to cancer (behind lung cancer) in the US by the year 2030. For good reason, then, November is Pancreatic Awareness Month. Several recent research items are of particular interest to us. Continue reading
MET – an ideal target for antibody drug conjugate therapy, plus nivolumab
MET is a gene that encodes a receptor tyrosine kinase that is activated upon binding with hepatocyte growth factor (HGF, or Scatter Factor). Specifically, MET is a Continue reading
CANTOS trial of canakinumab demonstrates that inflammation is a lung cancer promoter
Cells need to accumulate multiple mutations in order to induce the 10 hallmarks of cancer: Continue reading
Sitravatinib plus nivolumab in NSCLC
Sitravatinib (MGCD516) is an oral multi-tyrosine kinase inhibitor being developed by Mirati Therapeutics. Last week, the company announced that three of eleven patients with non-small cell lung cancer (NSCLC) with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL who were resistant to checkpoint [anti PD-(L)1 therapy] had confirmed partial responses; because of this, dosing in the 34-patient expansion cohort will proceed. Continue reading
New Link’s Indoximod + Keytruda looks promising in Phase 2 advanced melanoma
Indoximod + Keytruda looks promising in Phase 2 advanced melanoma
IDO (indoleamine-2,3-dioxygenase) is an intracellular enzyme found in antigen presenting cells that mediates immune suppression in the tumor microenvironment. Continue reading