Arovella Therapeutics confirms anti-tumour effect of lead drug ALA-101 in treating certain cancers
Relatively low doses of ALA-101 have “significantly” expended the lifespan of mice models with aggressive human B-Cell acute lymphoblastic leukemia.
Arovella Therapeutics (ASX: ALA) has presented new data at the American Association for Cancer Research annual meeting relating to lead drug ALA-101 as a novel ‘off-the-shelf’ therapy to treat CD19-expressing leukemias and lymphomas.
The data presented used iNKT (invariant natural killer) cells expressing a chimeric antigen receptor (CAR) which targets the CD19 biomarker.
The cells were manufactured using the ALA-101 third-generation lentiviral vector manufactured by Lentigen Technology Inc.
It is considered safer than previous lentiviral systems and is expected to pass regulatory requirements more easily as Arovella seeks to initiate first-in-human clinical trials.
ALA-101 cells
During manufacture, ALA-101 cells can be expanded up to 5,000 times while still retaining their functionality.
A high level of expansion is critical for producing multiple clinical doses of iNKT cells from a single batch.
ALA-101’s expansion ability is able to reduce costs and enables its use as an efficient, off-the-shelf product for cancer treatment.
Producing ALA-101 using this method displays robust killing of multiple CD19-expressing tumour cell lines, including cell lines which do not express CD1d gene.
It also eliminated more than 90% of viable cells expressing CD19 in a lymphoma patient sample.
Arovella’s data also demonstrated that ALA-101 cells retain their ability to multiply in response to CD19, as binding of the CD19 target on tumour cells promoted further expansion of the ALA-101 cells.
This antigen-induced proliferation is expected to occur when ALA-101 cells bind to tumour cells in a patient’s bloodstream, thereby enhancing the persistence of the cells and potentially improving efficacy.
Mouse model results
A relatively low dose of ALA-101 was found to be effective in an aggressive NSG (immunodeficient) mouse model of human B-cell acute lymphoblastic leukemia (B-ALL).
Tumour burden after 26 days in animals treated with ALA-101 was approximately 90% lower than in the untreated control animals.
ALA-101 also significantly enhanced the survival of the mice over untreated controls.
The model used tumour cells originating from a patient with an aggressive form of B-ALL.
Arovella said the data indicated that ALA-101 had potential to be a novel, ‘off-the-shelf’ cell therapy to treat certain leukemias and lymphomas.