Overcoming resistance to standard CD19-targeted CAR T using a novel triple antigen targeted vector

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Grant Award Details

Grant Number:
TRAN1-13996
Investigator(s):
Award Value:
$3,869,061
Status:
Active

Progress Reports

Reporting Period:
Final Operational Milestone #4

Grant Application Details

Application Title:

Overcoming resistance to standard CD19-targeted CAR T using a novel triple antigen targeted vector

Public Abstract:
Translational Candidate

A tri-specific chimeric antigen receptor (CAR) T cell product that will prevent relapse since targets 3 different tumor antigens

Area of Impact

Relapse associated with single or double antigen-targeted CAR T cells

Mechanism of Action

By being able to target 3 different tumor antigens simultaneously on a single CAR product, there is much less of a chance the tumor evasion associated by loss of a single antigen and relapse will occur.

Unmet Medical Need

Relapse from cancer due to antigen loss is considered a major impediment for CAR therapy. Further, by having one vector which can target all three major tumor antigens, this vector could be more widely applicable for many B cell malignancies.

Project Objective

Data needed for pre-IND filing

Major Proposed Activities

  • Determine the efficiency, stability and reproducibility of the DuoCAR vector on T cell transduction
  • Determine the specificity and efficacy of the DuoCAR T product versus conventionally used CD19 CAR T cells
  • Determine any potential off-target effects or toxicities of the DuoCAR T product using a closed GMP manufacturing system
Statement of Benefit to California:
Experience with commercial CAR-T products has identified that access to CAR-T therapy is a key bottleneck to equitable use of this life-saving intervention. The other major issue is efficacy and cancer relapse. UC Davis has the largest geographic catchment of any UC Medical Center enabling it to play a crucial role in enhancing California patient participation in stem cell trials. Development of a tri-specific vector also increases patient use by targeting a broader array of B cell cancers.