Defence Therapeutics has announced groundbreaking news about the development of a novel anti-cancer cellular vaccine using reprogrammed mesenchymal stromal cells.
Defence Therapeutics Inc., a Canadian biopharmaceutical company specialising in the development of immune-oncology vaccines and drug delivery technologies, has reported the development of a novel anti-cancer cellular vaccine by reprogramming the unconventional suppressive mesenchymal stromal cells (MSCs) into potent antigen presenting cells (APCs).
The immune system is a structured entity working in tandem to activate specific immune cells as a means to seek and destroy “non-self” antigens. With respect to cancer, the immune system relies on dendritic cells (DCs), a subset of potent endogenous APCs, to prime cytotoxic T lymphocytes (CTLs). CTLs can then attack and eliminate virally-infected or cancerous cells. Unfortunately, however, most cancer cells can acquire strategies to escape DC-elicited immunity resulting in the development of deadly tumours. Although several strategies were developed by other companies and tested to correct this abnormality, most of them failed due to limitations related to inefficient CTL priming.
To overcome this issue, Defence Therapeutics applied a novel strategy, which consists of reprogramming the immune-suppressive MSCs to convert them into potent APCs. This discovery and the application are not only unconventional, but it has the potential to revolutionise the field of modern medicine as it applies to novel therapeutic cancer vaccines and infectious diseases vaccines. This application discovered that it uses a unique cell type to which tumour cells are not programmed to respond. The advantage is substantial as mesenchymal stromal cells are logistically easier to produce and manufacture compared to conventional DCs.
Groundbreaking discovery using AccumTM technology
Defence’s technology platform is AccumTM. The variant A1 is a variant molecule within the AccumTM platform. This molecule A1 can form aggregates when admixed to a given antigen.
Dr Nehme Hachem is a computational biologist and pharmacogenomics expert specialising in analysing large chemo-genomic datasets. Dr Hachem has stated that A1 converts mesenchymal stromal cells into APCs by stimulating endoplasmic reticulum stress caused by the A1-antigen aggregates captured by treated cells. Furthermore, A1 could enhance antigen presenting properties by regulating several genes involved in lipid homeostasis, which has been reported to play a role in inflammation and immune reprogramming. As a result, A1-Reprogrammed MSCs (ARMs) activate a cellular defence mechanism known as the unfolded protein response, which has a single objective: to get rid of or destroy these toxic protein aggregates via the cellular proteasomal machinery. As such, antigen-pulsed ARMs elicit powerful anti-tumoral CTLs in response to presented peptide fragments.
Pre-clinical studies in animals show positive results
Defence conducted pre-clinical studies in animals which have recently shown that administration of the ARM vaccine along with the immune-checkpoints anti-PD1 results in a synergistic effect leading to 100% survival of animals with pre-established lymphoma.
“This is yet another clear successful example of how versatile and ecfficient the AccumTM technology is. By optimising specific components of the AccumTM molecule, Defence can expand and design new entities exhibiting novel pharmacological properties that can be used in the development of new products targeting various cancer indications on a personalised medicine approach”, said Sebastien Plouffe, the CEO of Defence Therapeutics.
Defence is currently preparing the manufacturing of the ARM vaccine in a GLP clean room in Canada in preparation for a Phase I trial in patients with melanoma. The objective is to start this clinical trial in Q2 of 2023.
