Lgr5-mediated self-renewal in B cell selection and leukemia-initiation

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Grant Award Details

Grant Number:
Human Stem Cell Use:
Award Value:

Progress Reports

Reporting Period:
Year 2

Grant Application Details

Application Title:

Lgr5-mediated self-renewal in B cell selection and leukemia-initiation

Public Abstract:
Research Objective

LGR5-antibody drug conjugate to target LIC in B cell tumors that undergo self-renewal


LIC were only defined in myeloid leukemia, while LIC populations in B cell tumors remain elusive. LICs give rise to drug-resistance and relapse and remain unsolved clinical problems in B cell tumors.

Major Proposed Activities

  • Proof of concept studies- Positive selection by antigen-receptor (BCR) signals drives self-renewal in normal B cell development and leukemia and lymphoma.
  • Define patient groups and B cell leukemia and lymphoma subtypes that will benefit from LGR5-ADC mediated eradication of LIC.
  • Safety and efficacy profiles - choice of LGR5-ADC based on safety and efficacy profiles in quiescent Lgr5+ populations
  • In vivo testing platform –optimizing LGR5-ADC efficacy and therapeutic window
  • IND-enabling studies, concept for multicenter phase 1 clinical trial to test safety and tolerability of LGR5-ADC in patients woth pre-B ALL and mature B cell lymphoma.
Statement of Benefit to California:
B cell tumors account for an estimated ~129,000 newly diagnosed patients in 2015 in the US and California. Despite improvements, survival rates recently leveled off near 60%. 40,000 patients are expected to die from B cell tumors in the US and California this year. 1.2 million people are currently living with or recovering from B cell tumors. Therefore, stem cell-based efforts to reduce toxicity and minimize late effects are an important aspect in the development of new therapy strategies.