Work

59P Long term survival data from all recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treated with MVX-ONCO-1 during open-labelled phase I and phase IIa clinical trials

Year: 2024

Type: article

Abstract: Background: CAR T cell therapies have shown success in cancer treatment, especially in hematologic malignancies.However, scalability, manufacturing, and inpatient treatment limit their broad use.A non-viral, off-the-shelf solution is key to overcoming these barriers, especially for indications outside oncology.Building on mRNA LNPs for in-vivo CAR T delivery, we developed SENDER (Specific Engager Nanoparticle DelivERy), a novel approach to redirect LNPs for targeted mRNA delivery to immune cells.SENDER proteins non-covalently bind to LNPs, redirect them to T cells, and block protein corona formation, reducing off-target accumulation in the liver.Methods: The SENDER technology delivers LNP to T cells, ensuring specific mRNA delivery while preventing off-target accumulation.The design was tested both in vitro, for its ability to deliver mRNA payloads to T cells, and in vivo, using a humanized mouse model to evaluate tumor clearance and CAR T cell expression.Results: CD3-targeting SENDER proteins effectively transfected both CD4 + and CD8 + T cells, while CD8-targeting SENDER proteins transfected only CD8 + T cells.The SENDER platform demonstrated superior targeting capabilities, allowing efficient mRNA delivery of multiple CARs and armoured elements to T cells.In a Nalm6 xenograft model, repeated doses of a novel humanised anti-CD19 mRNA CAR delivered via SENDER-LNPs resulted in rapid and sustained tumor clearance, achieved with a fraction of the dose typically required for other LNP targeting approaches.Off-target delivery to the liver was significantly reduced, highlighting the efficiency of the SENDER platform.Conclusions: -The SENDER platform enables targeted in situ CAR T cell generation via non-viral mRNA delivery whilst avoiding lymphodepletion -Approach allows for the redirection of LNPs specifically to T cells, reducing off-target effects -In vivo studies demonstrated rapid and sustained tumor clearance with a lower -dose of LNPs compared to other targeting methods.-Technology offers a scalable, redosable alternative to conventional CAR T therapies -The modular nature of SENDER allows adaptation for various therapeutic areas, using different targeting proteins and payloads.

Source: Immuno-Oncology Technology

DOI: 10.1016/j.iotech.2024.100870