Novel Rejuvenated T Cell Immunotherapy for Lung Cancer
Grant Award Details
Grant Type:
Grant Number:
DISC2-08874
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$1,968,456
Status:
Closed
Progress Reports
Reporting Period:
Year 2
Grant Application Details
Application Title:
Novel Rejuvenated T Cell Immunotherapy for Lung Cancer
Public Abstract:
Research Objective
Through this project, we would like to evaluate how this T-iPSC-based immunotherapy that we have developed can eliminate lung cancer cells effectively in vivo using xenografted SCID mice.
Impact
This novel T-iPSC-based immunotherapy will provide another effective treatment for lung cancer and possible other malignancies by supplying unlimited number of young and active CTLs.
Major Proposed Activities
Through this project, we would like to evaluate how this T-iPSC-based immunotherapy that we have developed can eliminate lung cancer cells effectively in vivo using xenografted SCID mice.
Impact
This novel T-iPSC-based immunotherapy will provide another effective treatment for lung cancer and possible other malignancies by supplying unlimited number of young and active CTLs.
Major Proposed Activities
- Peptides synthesis for EGFR mutation hot spots and selection of the peptides with affinity binding assay
- Patient lung cancer/ blood cell culture and xenograft establishment in SCID mice for establishing tumor model
- Peptide responsive T cell selection, IPS induction and T cell redifferentiation and expansion (rejCTL) for cell-based immunotherapy
- transfusion of patient specific rejCTL cells into lung cancer grafted mice to treat tumors
- Evaluation of the efficacy of rejCTL cell therapy by observing tumor sizes in xenografted mice
- Statistical analysis and conclusion for this novel cell-based cancer treatment and contact FDA for initiation of a clinical trial
Statement of Benefit to California:
Lung cancer is known to cause the highest fatality rate. California State and citizens suffer similarly as the US and worldwide do. A fairly common HLA allele, e.g. HLA A0201 presents in up to 50% of California populations. Thus, we can provide an ‘off the shelf’ therapy for most of cancer patients. As a California based institute, we will succeed this research and pioneer this frontier cell- based immunotherapy, and conduct a possible clinical trial through CIRM funding.
Publications
- Nat Methods (2018): Efficient scarless genome editing in human pluripotent stem cells. (PubMed: 30504872)
- Methods Mol Biol (2019): Generation of Antigen-Specific T Cells from Human Induced Pluripotent Stem Cells. (PubMed: 30649763)
- Development (2019): Hematopoietic stem cell-independent hematopoiesis and the origins of innate-like B lymphocytes. (PubMed: 31371526)
- Cell Stem Cell (2019): Highly Efficient and Marker-free Genome Editing of Human Pluripotent Stem Cells by CRISPR-Cas9 RNP and AAV6 Donor-Mediated Homologous Recombination. (PubMed: 31051134)
- Methods Mol Biol (2019): Human iPSC Generation from Antigen-Specific T Cells. (PubMed: 31396928)
- Cell Syst (2017): Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity. (PubMed: 29073372)
- Exp Hematol (2019): Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion. (PubMed: 31874780)
- Methods Mol Biol (2019): Using the Inducible Caspase-9 Suicide-Safeguard System with iPSC and Bioluminescent Tracking. (PubMed: 31396943)