Grant Award Details
A cellular immunotherapy approach (candidate) that targets non-small cell lung carcinoma (NSCLC) with EGFR mutations, and colorectal cancer (CRC) with KRAS mutations.
Progress Reports
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Grant Application Details
- Novel Rejuvenated T Cell Immunotherapy for Lung Cancer
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
- 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
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
- Methods Mol Biol (2019) Using the Inducible Caspase-9 Suicide-Safeguard System with iPSC and Bioluminescent Tracking. (PubMed: 31396943)
- Methods Mol Biol (2019) Human iPSC Generation from Antigen-Specific T Cells. (PubMed: 31396928)
- Exp Hematol (2019) Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion. (PubMed: 31874780)
- 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) Generation of Antigen-Specific T Cells from Human Induced Pluripotent Stem Cells. (PubMed: 30649763)
- Nat Methods (2018) Efficient scarless genome editing in human pluripotent stem cells. (PubMed: 30504872)
- Cell Syst (2017) Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity. (PubMed: 29073372)