Category Archives: passive immunotherapy

Daratumumab effective in front-line multiple myeloma

Anti-CD38 monoclonal antibody daratumumab (Darzalex) is indicated for the treatment or patients with multiple myeloma that have failed prior treatment. CD38 is a Continue reading

Anti-APRIL Antibody BION-1301 for Multiple Myeloma

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. Plasma cells are B lymphocytes (B-cells) that have been activated to produce immunoglobulins. When plasma cells become cancerous, the produce copious amounts of immunoglobulins and proliferate in the bone marrow, causing crowding-out of other essential hematopoietic cells, leading to reduced numbers of functioning white blood cells (leukopenia leading to immunosuppression), red blood cells (anemia), and megakaryocytes (thrombocytopenia). Continue reading

CLEC12A – a novel target for AML and MDS

CLEC12 (C-Type Lectin Domain Family 12 Member A) is negative regulator of granulocyte and monocyte functioning. It is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. It is also known as Myeloid Inhibitory C-Type Lectin-Like Receptor and Dendritic Cell-Associated Lectin. CLEC12 is a cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases. Continue reading

CD-19 CAR T-cell gets unanimous ODAC recommendation and Blincyto wins full FDA approval – managing cytokine release syndrome

This week, the FDA Oncology Drug Advisory Committee provided a unanimous recommendation to Novartis’ tisagenlecleucel, a CAR (chimeric antigen receptor) T-cell therapy directed against CD19 for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).  In addition, the FDA granted full approval to Amgen for Blincyto (blinatumomab), a bispecific monoclonal antibody that targets CD19, for indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children. Blincyto received conditional approval in 2015 for this claim. 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

Ublituximab, a novel anti-CD20 Monoclonal Antibody for CLL

TG Therapeutics is developing ublituximab, and anti-CD20 monoclonal antibody for patients with CLL (Chronic Lymphocytic Leukemia). In a phase 3 study in patients with relapsed disease, the combination of ublituximab and ibrutinib (Imbruvica) was superior to ibrutinib, alone – the overall response rates were 80% and 47%, respectively. Continue reading

Juno Advances CAR T-cell CAR017 and Halts CAR015 in Non-Hodgkin Lymphoma

Juno Therapeutics is developing Chimeric Antigen Receptor (CAR) T-cells directed against B-cell antigen CD19 for the treatment of patients with B-cell lymphomas. The company has elected to halt the development of JCAR015 for Acute Lymphoblastic Leukemia (ALL) and proceed with JCAR017 for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the most common form of Non-Hodgkin Lymphoma (NHL), due to the development of cerebral edema and subsequent death of several patients with ALL enrolled in its phase 2 ROCKET trial, which has been suspended. 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

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

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