Tagrisso (osimertinib) is a kinase inhibitor indicated for patients with metastatic epidermal growth factor T790M mutation-positive lung cancer. It was approved under accelerated approval provisions in November 2015 on the basis of phase 2 trials demonstrating a combined overall objective response rate of 59%. Continue reading
Etinostat blocks Treg activity via FOXP3 suppression
Histone deacetylase (HDAC) inhibitors block the removal of acetyl groups from histone proteins. Since acetylation of histones puts chromatin in a more favorable condition for transcription, HDAC inhibitors maintain this favorable state. HDAC inhibitors have been approved for use in cutaneous T-cell lymphoma. They act by sustaining transcription of tumor suppressor genes, which leads to cell cycle arrest and apoptosis. Continue reading
Neratinib for breast cancer – the key is managing gastrointestinal toxicity
Neratinib is an irreversible tyrosine-kinase inhibitor of EGFR (epidermal growth factor receptor), as well as HER1, HER2, and HER4. It is being developed for patients with breast cancer. It blocks many signal transduction pathways that result in proliferation and invasion, leading to cell cycle arrest and apoptosis. (Figures 1 and 2). Continue reading
Engineering safety into CAR T-cells to address toxicities
Adoptive immunotherapy with engineered T-cells, for example, CAR T-cells (Chimeric Antigen Receptor) is associated with significant toxicities including cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis. CAR T-cells lack the ability to respond to signals that maintain immune homeostasis. For this reason, they are effective relentless killers of cells that express the target to which they have been programmed, however, at a safety cost. Continue reading
Opdivo combined with novel IL-2 prodrug immune stimulant
Bristol Myers Squibb (BMS) and Nektar Therapeutics announced a collaboration in which BMS’ PD-1 checkpoint inhibitor (Opdivo, nivolumab) will be combined with Nektar;s CD-122 agonist NKTR-214. Continue reading
How PD-1 abrogates the anti-tumor immune response
PD-1 inhibition (Figure 1) has quickly become a front-line therapy for non-small cell lung cancer and melanoma. Moreover, PD-1 and PD-L1 inhibitors are being tested in combination with other checkpoint inhibitors, targeted therapies, cancer vaccines, monoclonal antibodies, and other modalities. But, how does PD-1 blunt the anti-tumor immune response? Continue reading
Combined CA4P (Fosbretabulin) therapy in Cancer- Ashini R. Dias, Contributor
Malignant tumors cannot grow beyond a certain size without establishing blood supply to feed them with necessary nutrients and oxygen. The process of recruiting new blood vessels to the tumor is termed angiogenesis. Growth factors, mainly secreted by the tumor itself, induce angiogenesis; the most notable of these is vascular endothelial growth factor (VEGF), which helps endothelial precursor cells mature into neo-capillary forming, endothelial cells. These secrete other growth factors, like platelet derivative growth factor (PDGF), which attracts pericytes and vascular smooth muscle cells that, together, create the outer layers of capillaries. Continue reading
Photo-immunotherapy approaches for cancer
The NCI (National Cancer Institute) highlighted two photo-immunotherapy (PIT) approaches that employ antibodies conjugated to phthalocyanine dye IRDye 700DX (IR700). Continue reading
Celgene Acquires EngMab for BCMA Program
Celgene acquired EngMab for $600MM to enrich its programs targeting B-cell maturation antigen (BCMA) for the treatment of multiple myeloma. Celgene is exploiting BCMA in both CAR T (chimeric antigen receptor T-cell) and bispecific antibodies targeting CD-3 (Cluster of differentiation 3), Continue reading
Roche Signs $310MM Early Stage Deal with for mRNA Vaccines
Roche will be collaborating with BioNTech to develop personalized vaccines based on BioNTech’s mRNA products combined with Roche’s PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), which was approved for bladder cancer in May 2016. Continue reading