Hypoimmunogenic iPSC-derived TCR-NK cells for oncology

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Grant Award Details

Grant Number:
TRAN1-16023
Investigator(s):
Institution:
Type:
PI

Award Value:
$4,107,571
Status:
Pre-Active

Grant Application Details

Application Title:

Hypoimmunogenic iPSC-derived TCR-NK cells for oncology

Public Abstract:
Translational Candidate

iPSC-derived NY-ESO-1 TCR/IL-15 NK cells

Area of Impact

NK drug product homogeneity and engraftment/response durability will be improved by this hypoimmunogenic iPSC-TCR-NK therapy in cancer patients

Mechanism of Action

The MoA of the candidate involves engagement of NY-ESO-1-peptide-presented HLA-A*02 molecules on the surface of tumor cells in tissues by the NY-ESO-1-specific TCR on the iPSC-TCR-NK cells, NK activation, lysis & subsequent killing of tumor cells, and extension of patient life. The low levels of secreted IL-15 from the iPSC-TCR-NK cell also promotes in vivo expansion, persistence, and tumor remodeling towards a more immune effector cell permissive microenvironment.

Unmet Medical Need

While great strides have been made in the treatment of MM, there are no options for patients who have progressed on B cell maturation antigen-directed therapies. The outcome of relapsed/refractory MM, especially the triple-class refractory MM patients, (refractory to proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal) is dismal. They have an overall response rate of approx 30% and a median PFS of 3-6 months. Our therapy provides a necessary alternative for these patients.

Project Objective

Pre-IND meeting

Major Proposed Activities

  • GMP Activities - GMP edited iPSC generation, Master Cell Banking, GMP iPSC-TCR-NK drug product manufacturing
  • Animal studies (efficacy & pilot safety) & in vitro hypoimmunogenicity testing of GMP product with immune cells from donors from diverse populations
  • Pre-IND Meeting
Statement of Benefit to California:
This project will provide immediate benefit to the state by contributing to the employment & retention of skilled scientists, technicians, and engineers in California. In the medium term the project will attract funding through investment and partnerships to California contributing to the research economy. Long term, this project will transform patient care to a diverse population by enabling increased access to cancer cell therapies close to home.