|
AIVITA Biomedical, Inc., a biotechnology company developing personalized vaccines for the prevention of infectious disease and treatment of cancer, announced a new study published in Cell Stem Cell describing a universal, stem cell-derived dendritic cell platform that can be personalized to an individual patient’s tumour and used to train the immune system to attack cancer. The study, “Engineered Human iPSC-Derived Dendritic Cells Dressed with Tumour MHC Complexes as a Cancer Vaccine,” was led by senior author Robert Blelloch, M.D., Ph.D., of UC San Francisco (UCSF), and includes AIVITA’s Krystal Godding, Gabriel I. Nistor, M.D., and Hans S. Keirstead, Ph.D. among its authors (Cell Stem Cell).
The UCSF team engineered dendritic cells, the immune system’s primary antigen-presenting cells, from induced pluripotent stem cells (iPSCs) and used gene editing to remove the surface markers that would normally trigger immune rejection, creating an unlimited, “off-the-shelf” cell source. They then “dressed” these universal dendritic cells with the complete antigen signature carried on a patient’s own tumour cells, rather than a single synthetic target. The resulting dressed dendritic cells trained matched patient T cells to recognize and kill tumour cells from both blood cancer (leukaemia) and solid tumour samples, and slowed tumour growth in an animal model.
AIVITA’s contribution was central to extending this proof-of-concept from blood cancer into solid tumours. Drawing on de-identified tumor tissue and matched naive peripheral blood mononuclear cells (PBMCs) from ovarian cancer patients enrolled in AIVITA’s own Phase 2 clinical trial (ClinicalTrials.gov NCT00331526), AIVITA’s team grew and supplied the patient-specific tumour cells that gave UCSF’s dressed dendritic cells their antigen target and collaborated with the UCSF team throughout the studies that followed. T cells trained by dendritic cells dressed with this AIVITA-supplied material showed a marked increase in T-cell stimulation and killing of matched ovarian tumour cells, extending validation of the platform beyond blood cancer into solid tumours, the category at the centre of AIVITA’s own therapeutic pipeline.
“This study is an important external validation of a scientific thesis AIVITA has pursued since our founding: that a patient’s own tumour holds the most complete and personalized map of the antigens the immune system needs to see,” said AIVITA CEO Dr. Hans S. Keirstead. “The UCSF team has built an elegant, scalable way to put that map onto an unlimited supply of lab-grown dendritic cells.”
“Our pan-antigenic platform and UCSF’s dressing approach solve the same problem from two different angles: an unlimited, personalized supply of a patient’s true antigen repertoire,” said Gabriel I. Nistor, M.D., chief science officer at AIVITA. “We supplied the complete antigen signature of a real tumor rather than a single synthetic peptide, which is why the T-cell response was so strong.”
The study was supported by the National Institutes of Health (U01CA244452), the California Institute for Regenerative Medicine (DISC0-13806, EDUC4-12812), a NIH Cancer Moonshot Award, a Sandler Program for Breakthrough Biomedical Research New Frontiers Award, and the Benioff Initiative for Prostate Cancer Research (UCSF News).
Founded in 2016 by pioneers in the cell therapy industry, AIVITA Biomedical, Inc. utilizes its expertise in stem cell growth and directed, high-purity differentiation to enable safe, efficient and economical manufacturing systems which support its therapeutic pipeline.
|