Cancer and autoimmune disorders are opposite sides of the same coin – cancer is a result of hypo-active immunity, whereas, autoimmune diseases is the result of hyper-active immunity. This is dramatically illustrated in examining side effects in patients with melanoma who receive checkpoint therapy with ipilimumab (Yervoy), which acts in the early stages of T-cell activation and priming, and nivolumab (Opdivo), which acts in the later stages of T-cell activation in the tumor microenvironment. Continue reading
Category Archives: Immunology & Immunotherapy
PD-L1 Expression correlates with outcomes in patients with melanoma
Keytruda (pembrolizumab) and Opdivo (nivolumab) are monoclonal antibodies that disrupt the PD-1 (Opdivo) / PD-L1 (Keytruda) pathway; they are approved by the FDA for the treatment of patients with unresectable melanoma, as well as other cancers including non-small cell lung cancer (NSCLC), head and neck cancer, renal cell carcinoma (Opdivo), and Hodg kin lymphoma (Opdivo). Keytruda is limited to patients with NSCLC with a tumor proportion score (TPS) of greater than 50% for PD-L1 staining. Continue reading
BMS and PsoOxus collaborate on transgenic oncolytic virus plus nivolumab
BMS paid PsiOxus $50MM upfront for exclusive rights to develop PsiOxus’ NG-348 enadenotucirev, a systemically administered oncolytic adenovirus therapeutic, in combination with Bristol-Myers Squibb’s Immuno-Oncology checkpoint inhibitor Opdivo (nivolumab) to treat a range of solid tumor types in late-stage cancer patients. This is a “big deal” – PsiOxus could receive up to $886 million in development, regulatory, and sales-based milestones, plus sales royalties. Continue reading
Xencor’s Bispecific Antibodies in AML and B Cell Malignancies – Ashini R. Dias, Contributor
Most of the antibodies currently used in therapy are monospecific or monoclonal – they specifically target a particular part of an antigen, called an epitope. The heterogeneous nature of the cancer allows frequent mutations and cross-talk among multiple signaling cascades, which ultimately leads to uncontrollable growth and proliferation of the tumor. Thus, antibodies that bind to two different epitopes on the same or different antigens (known as bispecific) are conceptually superior to monoclonal antibodies. The “dual-target” functionality of the bi-specific antibody consisting of two variable domains allows it to bind to multiple surface receptors or ligands in signaling pathways. Although this phenomenon was identified 30 years back, the first bispecific antibody [Removab – catamuxumab: binds to epithelial cell adhesion molecule (EpCAM) on tumor cells the CD3 antigen on T-cells] was approved for therapy in 2009 in Europe for the treatment of malignant ascites after long years of research and development. 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
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