Preclinical Development of An HSC-Engineered Off-The-Shelf iNKT Cell Therapy for Cancer
Grant Award Details
Grant Type:
Grant Number:
DISC2-11157
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,404,000
Status:
Closed
Progress Reports
Reporting Period:
Year 2/NCE
Grant Application Details
Application Title:
Preclinical Development of An HSC-Engineered Off-The-Shelf iNKT Cell Therapy for Cancer
Public Abstract:
Research Objective
The expected outcome is a therapeutic candidate, allogeneic HSC-engineered HLA-I/II-negative human iNKT cells, that can potentially be used as an off-the-shelf cellular therapy for treating cancer.
Impact
The proposed off-the-shelf HSC-engineered iNKT therapy has the potential to become a general cancer immunotherapy for treating multiple cancers and a large population of cancer patients.
Major Proposed Activities
The expected outcome is a therapeutic candidate, allogeneic HSC-engineered HLA-I/II-negative human iNKT cells, that can potentially be used as an off-the-shelf cellular therapy for treating cancer.
Impact
The proposed off-the-shelf HSC-engineered iNKT therapy has the potential to become a general cancer immunotherapy for treating multiple cancers and a large population of cancer patients.
Major Proposed Activities
- Milestone 1: Production of the Universal HSC-Engineered iNKT (UHSC-iNKT) cells
(1. Generate lentivector; 2. Generate CRISPR; 3. Collect HSCs; 4. Engineer HSCs; 5. Produce HSC-engineered iNKT cells.) - Milestone 2: Characterization of the UHSC-iNKT cells
(1. Identity/activity/purity; 2. PK/PD; 3. MOA; 4. Efficacy; 5. Safety; 6. Combination therapy.) - Milestone 3: Delivery of the new therapeutic candidate
(1. Identify UHSC-iNKT cells as the new therapeutic candidate; 2. Develop a draft TPP; 3. Prepare for and conduct a pre-pre-IND meeting.)
Statement of Benefit to California:
iNKT cells have the remarkable capacity to target a broad range of cancers independent of tumor antigen- and MHC-restrictions. The proposed HSC-engineered off-the-shelf iNKT cellular product has the potential to benefit a large population of cancer patients at California who suffer from cancers that are subject to iNKT cell regulation, including solid tumors (melanoma, colon, lung, breast, and head and neck cancers) and blood cancers (leukemia, multiple myeloma, and myelodysplastic syndromes).
Publications
- Cell Stem Cell (2023): Advancing cell-based cancer immunotherapy through stem cell engineering. (PubMed: 36948187)
- Nat Commun (2025): Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies. (PubMed: 39893165)
- Cell Rep Med (2021): Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy. (PubMed: 34841295)
- Stem Cell Res Ther (2022): Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention. (PubMed: 35313965)
- Cells (2021): Development of Stem Cell-Derived Immune Cells for Off-the-Shelf Cancer Immunotherapies. (PubMed: 34944002)
- Mol Ther (2024): Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy. (PubMed: 38584391)
- Trends Pharmacol Sci (2024): Frontiers in CAR-T cell therapy for autoimmune diseases. (PubMed: 39147651)
- Nat Protoc (2025): Generating allogeneic CAR-NKT cells for off-the-shelf cancer immunotherapy with genetically engineered HSP cells and feeder-free differentiation culture. (PubMed: 39825143)
- Nat Biotechnol (2024): Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method. (PubMed: 38744947)
- iScience (2022): Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers. (PubMed: 36034226)
