Funding opportunities

Ensuring the safety of cell therapy: a quality control pipeline for cell purification and validation

Funding Type: 
Early Translational I
Grant Number: 
Principle Investigator: 
Funds requested: 
$6 292 290
Funding Recommendations: 
Grant approved: 
Public Abstract: 
Statement of Benefit to California: 
Review Summary: 
Potential teratoma formation resulting from residual human pluripotent stem cells (hPSC) in human embryonic stem cell- (hESC) or hiPSC-derived products is a bottleneck to the development of pluripotent cell-derived therapies. The applicant proposes to address this bottleneck by developing a toolbox and a process that would detect and remove hPSC from hPSC-derived cell therapy candidates prior to treatment of patients. The investigators will develop new antibody tools and cell purity assays with the goals of removing undesired cell types by antibody based methods and enriching for the desired cell type. There are four aims: 1) to develop monoclonal antibody- (mAb-) based methods to generate homogenous pluripotent stem cells; 2) to develop mAb-based methods to eliminate undesired pluripotent or differentiated cells from desired cell population; 3) to develop biomarker panels to evaluate the purity of pluripotent and differentiated cell types; and 4) to test the process using a well-studied hESC-derived cell population as a proof-of principle. The project involves collaboration between laboratories with expertise in human pluripotent stem cells (hPSC), molecular profiling, high throughput screening and antibody development. This proposal was well written and its translational focus was considered responsive to the RFA. Reviewers praised its detailed flow diagrams, well stated rationale, and clearly developed antibody development. Concern was expressed about the level of experimental co-ordination required of the collaborators to meet the ambitious proposed timelines; although the flow diagrams demonstrated that this difficulty and potential impact on the timelines had been considered. Recognition of the importance of removing potentially deleterious more differentiated cell types in addition to undifferentiated cells strengthens the proposal. This work has potential to generate a valuable toolbox that will benefit the stem cell community, including needed antibodies specific to pluripotent cell surface markers. The work will build upon and exploit the Principal Investigator’s (PI’s) unique database of cell type specific gene expression profiles to develop antibodies. Reviewers did comment that no tumorgenicity study appeared to be part of the proof of principle study to validate that the proposed process for removal of undesirable cells The PI is well established, familiar with translational and safety issues and capable of managing this large, multicenter project. The sponsoring institute has a rich, interactive environment. The co-PI has expertise in mAb generation. This multidisciplinary team brings appropriate expertise and facilities including antibody manufacture, stem cell culture, molecular profiling, assay development and screening to successfully pursue the project. The inclusion of a consultant on the team who has experience in interacting with the FDA was noted as an expertise that should have been included by many more of the applicants . All reviewers expressed concern at the inappropriate size of the proposal’s “enormous” budget. Given the scope and nature of the work, the overall budget was judged to be excessive, and not sufficiently justified. Reviewers pointed out the large number of requested personnel with little articulated justification for their roles on the project. Additionally, the consumables expense category was noted to be very high. In summary, this proposal addresses the teratoma bottleneck to hPSC cell therapy development by establishing a toolbox and a workflow to remove residual pluirpotent stem cells from differentiated cell products for therapy . In addressing the teratoma bottleneck, reviewers felt that this program will result in needed tools that will benefit the entire stem cell community but had reservations about the cost of the program given the proposed deliverables.

© 2013 California Institute for Regenerative Medicine