2024-03-05
Using ‘iTANK’ bacterial transgene to target heterogenous solid tumour environments
In January 2024 the new CAMP project “Fully closed (from vein to vein) automated CAR-T manufacturing process” was initiated. With Uppsala University as the lead partner, the project aims to fully close manufacture of project partner Elicera Therapeutics’ drug candidate ELC-401, an IL13Ra2 targetting CAR T for glioblastoma, combined with the iTANK-technology. The closed and automated manufacturing process will be developed in partnership with Vecura at the Karolinska University Hospital.
In 2022, Elicera was awarded a Vinnova grant for a project to develop an automated process for CAR T-cell manufacturing for drug candidate ELC-301, a CAR T-cell therapy targeting CD20 for B cell lymphoma patients relapsing after CD19 CAR T-cell treatment. While automated, the process developed for ELC-301 still had semi-open handling steps at cell separation, virus loading and formulation (Figure 1). This new CAMP project aims to close those semi-open handling steps to improve quality and minimise product loss or manufacture failure due to introduced infection or operator error. The total manufacturing time is also expected to be reduced. Studies show that quicker treatment for this indication gives better patient outcomes (REF).
Elicera’s CEO Jamal El-Mosleh says this project is about ensuring patient access, “the quicker we can get the cells back to the patient, the less likely they are to die waiting for treatment. The more we minimise production related failures, the more likely the patient is to receive this potentially lifesaving treatment”.
Figure 1: Manufacturing process developed for ELC-301 in the Vinnova project
The strategy for closing the semi-open steps above includes;
The project will run till December 2024, the end of the CAMP project funding. Pontus Blomberg, Director at the Karolinska Cell Therapy Centre says, “we have been producing CAR T cells for clinical trials at Vecura since 2014. Collaborating with Elicera and Uppsala University to evolve their manufacture platform has been a great experience and we are pleased to have another opportunity through this CAMP project. GMP manufacture in this space is all about the highest possible quality and lowest risk for patients, this CAMP project addresses multifaceted improvements in both”.
Learn more about the CAMP project, including contact details, here; Fully closed (from vein to vein) automated CAR-T manufacturing process
The retrovirus delivered to make Elicera’s ELC-401 autologous patient cells contains both chimeric antigen receptor (CAR) and ‘iTANK’ transgenes, a strategy optimised to fighting solid tumours. The CAR homes the cells to the tumour and enables killing of CAR antigen positive cells (1 in Figure 2). Upon CAR binding to the tumour, the engineered cells begin to express the iTANK transgene, producing the ‘NAP’ bacterial protein (2) that triggers an inflammatory process that recruits endogenous immune cells to the tumour (3). These immune cells then begin to attack and kill tumour cells in proximity to the CAR T (4) enabling phagocytosis of tumour debris by dendritic cells (5) that then stimulate the patient immune system to produce tumour antigen specific T cells (6/7/8). This two-pronged attack combines CAR T dependent killing by engineered patient cells with CAR independent killing by endogenous, unengineered T cells. This enables a unique mechanism to infiltrate and kill heterogenous solid tumour microenvironments.
Figure 2: Schematic of mechanism of action of the combined CAR and ‘iTANK’ transgene strategy as used in ELC-401
ABOUT ELICERA
Elicera was founded in 2014 with 4 drug candidate assets, the 2 CAR Ts mentioned above and 2 oncolytic virus technologies. These technologies came from the research of Magnus Essand and Di Yu at Uppsala University. Jamal El-Mosleh joined Elicera in 2020 with the competencies needed to commercialise the candidates. The company has been successful at receiving grants and soft funding and an EIC accelerator fund EU grant for their ELC-301 B cell lymphoma program. They have a rights issue to fund the rest of their trials and to commercialise the iTANK-platform. The company is expected to initiate the clinical phase I/IIa trial CARMA with ELC-301 in a total of 18 cancer patients in the first half of 2024.