On September 2nd, Tiziana Life Sciences PLC (NASDAQ:TLSA) (LSE:TILS) announced an exclusive licensing agreement with Precision BioSciences (NASDAQ:DTIL) for the exploration and development of foralumab as a lymphodepletion agent to complement Precision’s CAR T therapy portfolio.
Since our last update, Tiziana also formally declared the start of its corporate reorganization to a Bermuda-incorporated company that will trade exclusively on the NASDAQ, and published an article detailing results from Tiziana’s trial of foralumab in mild to moderate COVID-19 patients in Brazil.
Anti-CD3 and CAR T: Joining with Precision
On September 2, 2021, Tiziana announced that it had entered into an exclusive licensing agreement with Precision BioSciences (NASDAQ:DTIL) to evaluate Tiziana’s foralumab in conjunction with Precision’s allogeneic CAR T portfolio. In this arrangement, foralumab, an anti-CD3 fully human monoclonal antibody, is being investigated as a lymphodepletion agent, an agent that purposely destroys the patient’s immune system, including T cells, to make way for CAR T cells. Lymphodepletion is performed before receiving adoptive cell therapy (ACT).
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The aim is to determine whether or not foralumab can improve the outcome of ACT. Lymphodepletion typically comprises short-course chemotherapy to destroy T, B and NK cells. This can have the effect of debulking the tumor, altering the tumor phenotype, modifying the tumor microenvironment, and modulating the cytokine profile.1 Common lymphodepletion agents include fludarabine and cyclophosphamide, typically used in combination.
These agents have severe side effects and in the case of fludarabine, are associated with neurotoxicity. Foralumab has the potential to either replace or reduce the chemotherapy regimen, thereby improving the side effect profile for patients.
Foralumab may induce tolerance of allogeneic CAR T, or CAR T cells not from the patient’s own body, but from a donor, which may attack the patient (host) in what is known as graft-versus-host-disease (GVHD). Allogeneic CAR T has advantages over autologous approaches in that generation of autologous CAR T cells can be challenging, especially in patients of advanced disease due to the length of time needed to generate the cells.2
