CD19 CAR-T
CD47/CD19
BTK
PD-L1
CD20
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Azercabtagene zapreleucel (“azer-cel”) is an investigational anti-CD19 allogeneic chimeric antigen receptor (CAR) T cell therapy. In contrast to autologous CAR T cell therapies which are made individually from a patient’s own cells, azer-cel is an allogeneic or “off-the-shelf” therapy made from donor-derived T cells, modified using a proprietary genome editing technology. Azer-cel recognizes the well characterized B cell surface protein CD19 and is designed to avoid graft-versus-host disease, a significant complication associated with other donor-derived, cell-based therapies.
TG-1801 is an investigational first-in-class, bispecific anti-CD47/CD19 monoclonal antibody. It is the first therapy to target both CD19, a B-cell specific marker widely expressed across all B-cell malignancies, and CD47, the “do not eat me” signal used by tumor cells to evade macrophage-mediated phagocytosis, or ‘tumor cell eating’. CD47 is also expressed ubiquitously on normal cells, including red blood cells and platelets, where it helps to regulate the renewal of these cells in the body. The CD19 component is designed to improve the targeting of TG-1801 to malignant cells that express CD19, which would preempt binding of the bispecific antibody to normal cells expressing CD47 In addition, the targeting of CD19 provides a secondary mechanism of direct anti-tumor activity through the engagement of effector cells and induction of antibody dependent cellular cytotoxicity (ADCC). By targeting both CD19 and CD47, TG-1801 offers the prospect of killing the tumor cell through each of these two distinct mechanisms.
In preclinical assays, TG-1801 has demonstrated a potent ability to induce antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) of malignant B-cell lines and primary tumor B-cells from patients with acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL). and numerous other subtypes of NHL.
A first-in-human phase 1 study of TG-1801 is ongoing in patients with B-cell lymphoma.
Please click here to view currently available clinical trials for TG-1801.
Please click here to view our Publications Page.
TG-1701 is an investigational oral, once-daily BTK inhibitor that irreversibly binds to and inhibits Bruton’s tyrosine kinase (BTK), a crucial driver of B-cell proliferation.
B-cell receptor (BCR) signaling drives normal B-cell development and supports the growth and survival of malignant B-cells. Targeting BTK has been validated as an important therapeutic strategy for select B-cell malignancies including CLL and NHL.
A phase 1 study evaluating TG-1701 as a single agent alone and in combination with ublituximab and umbralisib in patients with CLL and NHL is ongoing.
Please click here to view currently available clinical trials for TG-1701.
Please click here to view our Publications Page.
TG-1501 (cosibelimab) is an investigational fully humanized monoclonal antibody that binds to the programmed death-ligand 1 (PD-L1) and blocks its interactions with PD-1. It has been well established that cancer cells can evade anti-tumor immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Signals from PD-L1 on tumor cells and in the tumor microenvironment help those tumors avoid immune mediated elimination by preventing activation of tumor-specific effector T-cells. Anti-PD-L1 antibodies are designed to block that signal, permitting effector T-cells to attack and eradicate the cancer.
Despite the demonstrated activity of anti-PD-L1and PD-1 therapy across a variety of cancers, there is limited clinical trial experience with this class of drugs across different types of B-cell cancers such as Non-Hodgkin’s Lymphoma (NHL) and chronic lymphocytic leukemia (CLL), which is the focus of our team.
Preclinically, it has been shown that the effects of anti-PD-L1 can be enhanced by other drugs which have a complementary effect on the tumor microenvironment, like targeting CD20 and CD47 for example, which may render the malignant cells more vulnerable to the host immune system. Based on this preclinical data, we are exploring combination regimens in an effort to optimize the effects of the anti-PD-L1 antibodies against B- cell lymphomas and CLL.
Please click here to view currently available clinical trials for TG-1501.
Please click here to view our Publications Page.
Ublituximab is an investigational glycoengineered monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. When ublituximab binds to the B-cell it triggers a series of immunological reactions (including antibody-dependent cellular cytotoxicity [ADCC] and complement dependent cytotoxicity [CDC]), leading to destruction of the cell. Additionally, ublituximab is uniquely designed, to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, has been shown to enhance the potency of ublituximab, especially the ADCC activity.
Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of B-cell malignancies and autoimmune disorders, both diseases driven by the abnormal growth or function of B-cells.
Ublituximab is being evaluated in pivotal trials for patients with relapsing forms of multiple sclerosis (RMS).
Please click here to view our Publications Page.