- Human CAR-M cells can be generated with the pan-amyloid reactive p5 peptide as the target amyloid recognition element
- This novel system may serve as an adjunct to anti-amyloid monoclonal antibodies for the enhanced clearance of tissue amyloid
SAN FRANCISCO, Calif. – September 6, 2022 – Attralus, Inc., a clinical stage biopharmaceutical company developing transformative medicines to improve the lives of patients with systemic amyloidosis, today announced exciting new preclinical data from the University of Tennessee Graduate School of Medicine from its study on novel human chimeric antigen receptor-macrophages (CAR-M) as a potential therapeutic for amyloid clearance. The data was included in an oral presentation at the 18th International Symposium on Amyloidosis (ISA) taking place September 4-8, 2022, in Heidelberg, Germany.
Data presented at ISA demonstrates a novel use of the Company’s pan-amyloid removal (PAR) technology in which human CAR macrophages incorporate the pan-amyloid reactive p5 peptide as the amyloid-binding moiety. The p5 peptide is related to the basic peptide used in the Company’s diagnostic agent, AT-01 (iodine (I-124) evuzamitide), as well as its therapeutic candidates AT-02 and AT-04. Expression of the CAR in human THP-1 cells enhanced phagocytosis of human amyloid extracts and has the potential to serve as a standalone therapy or as an adjunct to other PAR therapeutics to enhance the removal of amyloid.
“The use of amyloid-reactive CAR-M is an exciting novel approach to facilitate the macrophage-mediated removal of systemic amyloidosis,” said Gregory Bell, MD, Chief Medical Officer at Attralus. “We are excited to explore more opportunities to potentially transform the treatment of these diseases and improve the lives of patients.”
- Human CAR-M cells can be generated with the pan-amyloid reactive p5 peptide as the target recognition element.
- THP-1 cells were successfully transduced with lentiviral particles carrying the amyloid-reactive CAR construct.
- Expression of these receptors results in plasma membrane insertion and enhanced phagocytosis of amyloid substrates as compared to native macrophages.
- Pools of transduced cells and single cell clones were generated that exhibited positive cytoplasmic and cell surface staining of the human Fcg, indicating expression and insertion of the CAR into the plasma membrane in the correct orientation.
- PMA-activated CAR-M cells phagocytosed pHrodo-labelled synthetic rVl6WIL fibrils and human AL and ATTR amyloid extracts significantly better than native THP-1 cells as evidenced by the enhanced pHrodo red fluorescence emission, with more than a two-fold increase in phagocytosis compared to control THP-1 cells for most substrates.
- This effect was further significantly enhanced by the presence of an amyloid-reactive opsonin (antibody-peptide fusion) and 20% human serum as a source of complement.
- This novel system may serve as a new modality for the clearance of tissue amyloid.
“We have seen the innovations in CAR-T and CAR-M approaches to the treatment of cancers. We were eager to see if the same concept could be used to promote phagocytosis of amyloid,” said Jonathan Wall, Ph.D., Distinguished Professor, University of Tennessee Graduate School of Medicine. “We are enthusiastic about our ability to leverage the PAR technology in new and innovative ways, in this case cell therapy.”
Oral Presentation Details
Abstract Title: Development of novel human chimeric antigen receptor-macrophages (CAR-M) as a potential therapeutic for amyloid clearance
- Presented by: Manasi Balachandran, Ph.D., Assistant Professor, University of Tennessee Graduate School of Medicine
- Session: Scientific Session: Basic Research – New Treatment Targets and Biomarkers
- Date/Time: September 6, 2022, 10:30 a.m. – 12:05 p.m. CEST
For additional information, please visit the ISA 2022 website.
About CAR-M PAR Therapeutic
CAR-M is a fusion of Attralus’s pan-amyloid reactive p5 peptide as the amyloid binding moiety and human chimeric antigen receptor-macrophages. The proprietary peptide binds to all types of amyloid and delivers the CAR-M to the site of disease to stimulate the immune system to remove amyloid. The same PAR-peptide technology is utilized in other Attralus therapies and diagnostics.
About Systemic Amyloidosis
Systemic amyloidosis encompasses a diverse group of rare diseases that occur due to accumulation of toxic amyloid deposits in tissues and organs, a consequence of aberrant protein misfolding events. These diseases are progressive, debilitating and often fatal. Systemic amyloidosis is significantly underdiagnosed due to low awareness, lack of specific symptoms, and no current disease-specific diagnostics. The two most common forms of systemic amyloidosis are immunoglobulin light-chain-associated (AL) amyloidosis and transthyretin-associated amyloidosis (ATTR). There is a significant unmet need for new therapies and diagnostics in systemic amyloidosis.
Attralus is a clinical stage biopharmaceutical company focused on creating transformative medicines to improve the lives of patients with systemic amyloidosis. The company’s proprietary pan-amyloid removal (PAR) therapeutics are designed to directly bind to and remove toxic amyloid in organs and tissues. By targeting the universal disease-causing pathology in systemic amyloidosis diseases, PAR therapeutics have the potential to treat and reverse disease in patients with all types and stages of systemic amyloidosis. Attralus was founded by scientific experts in the field of amyloidosis and the company is headquartered in San Francisco.
This press release contains forward-looking statements, including statements related to the efficacy, continued development, and potential of CAR-M. Words such as “novel,” “developing,” “first and only,” “potential,” “shown” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Attralus’ current expectations. Forward-looking statements involve risks and uncertainties. Attralus’ actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Attralus expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Attralus’ expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based.