Category Archives: Heterotypic Cellular Interactions

Anti-GARP: Combatting Treg Cells and TGF-β in the Tumor Microenvironment

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

Adenosine – a critical checkpoint in the tumor microenvironment

The tumor microenvironment (TME) includes a host of cells (mesenchymal, immune, vascular), cytokines, and other signaling molecules that serve to abrogate the innate and adaptive immune responses against the tumor. This is appropriate to maintain tissue homeostasis, and to prevent autoimmunity after the rogue cancer cells have been eliminated. Cancer cells co-opt many of these pathways to terminate the effective immune response so that they are not wiped out, rather, proliferate, invade, metastasize and kill, 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

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

Priming cancer for immunotherapy

Augmenting the responses to checkpoint inhibitors, which remove the “breaks” from the immune response, is a very popular area of research. The general concept is to turn immunologically cold tumors hot. For example, triple negative breast cancer (TNBC) is considered an immunologically cold tumor – anti-PD(L)1 therapy has shown responses of just 5-10%. 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

OLIG2 inhibitor for glioblastoma

OLIG2 (Oligodendrocyte transcription factor-2) is a transcription factor that is expressed in the pMN domain of the ventral ventricular zone in the embryonic spinal cord. Along with OLIG1, it is responsible for the development of motoneurons and oligodendrocytes. Astrocytes and ependymal cells also originate from the pMN domain. Continue reading

CARMA – Chimeric Antigen Receptor Macrophages

CARMA Therapeutics, a company that develops chimeric antigen receptor technology, not for T-cells (CAR-T cells), rather, for macrophages, hence the name “CARMA,” closed on an initial round of funding to advance its technologies. Continue reading