A First-in-Class Treatment for Progressive Multifocal Leukoencephalopathy Via Multimodal Immune System Engineering
Grant Award Details
Grant Type:
Grant Number:
DISC2-14907
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$2,182,396
Status:
Active
Grant Application Details
Application Title:
A First-in-Class Treatment for Progressive Multifocal Leukoencephalopathy Via Multimodal Immune System Engineering
Public Abstract:
Research Objective
We propose to discover genome- and epigenome-edited allogeneic T cells engineered to selectively target JCV as a potentially lifesaving treatment for progressive multifocal leukoencephalopathy (PML).
Impact
If successful, we would revolutionize treatment for PML patients in whom T cell immunity cannot be restored or boosted and unable to wait for adoptive transfer of donor-derived cell-based therapies.
Major Proposed Activities
We propose to discover genome- and epigenome-edited allogeneic T cells engineered to selectively target JCV as a potentially lifesaving treatment for progressive multifocal leukoencephalopathy (PML).
Impact
If successful, we would revolutionize treatment for PML patients in whom T cell immunity cannot be restored or boosted and unable to wait for adoptive transfer of donor-derived cell-based therapies.
Major Proposed Activities
- In vitro evaluation of JC virus-specific TCRs
- Multiplex engineering to develop an allogeneic T cell product
- Epigenome editing of T cell product to enhance on-target potency
- In vivo evaluation of engineered JC virus-specific TCRs
- Identify additional JCV virus-specific TCRs for ethnically diverse HLA-A haplotypes
- Isolate and evaluate high affinity TCRs to expand capacity of therapeutic opportunities
Statement of Benefit to California:
The proposed research will benefit the State of California and its citizens by developing a therapy accessible to patients of diverse backgrounds. While our focus is to develop an allogeneic T cell therapy for PML, once the bench-to-bedside therapeutic pipeline is built, it can be leveraged to develop therapeutics for other neuroinflammatory diseases with antigen-specific, CRISPR-engineered cell therapies, offering neurologic patients a potentially effective and curative therapy.