Targeting multiple myeloma with BCMA-CAR NK cells expressing a GPRC5D-NKG2D bispecific antibody
Grant Award Details
Grant Type:
Grant Number:
TRAN1-14716
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$6,036,001
Status:
Active
Grant Application Details
Application Title:
Targeting multiple myeloma with BCMA-CAR NK cells expressing a GPRC5D-NKG2D bispecific antibody
Public Abstract:
Translational Candidate
s15.BsAb.BCMA-CAR NK cells derived from CD34(+) umbilical cord blood hematopoietic stem cells
Area of Impact
patients with multiple myeloma
Mechanism of Action
s15.BsAb.BCMA-CAR NK cells are umbilical cord blood-derived CD34+ hematopoietic stem cells that are engineered to include two components of the BCMA-CAR and the anti-NKG2D-anti-GPRC5D BsAb. s15.BsAb.BCMA-CAR NK cells can launch dual targeting of both BCMA and GPRC5D antigens expressed on the surface of MM and produce two living agents, CAR NK cells and BsAb, to eradicate MM cells effectively.
Unmet Medical Need
Although BCMA-CAR T cells have been approved by the FDA, MM is still an incurable disease. BCMA-CAR T cells show good response, but most patients eventually relapse. Patients treated with BCMA CAR-T cells experience cytokine release syndrome (CRS) and neurotoxicity.
Project Objective
Complete Pre-IND submission and finalize IND plans
Major Proposed Activities
s15.BsAb.BCMA-CAR NK cells derived from CD34(+) umbilical cord blood hematopoietic stem cells
Area of Impact
patients with multiple myeloma
Mechanism of Action
s15.BsAb.BCMA-CAR NK cells are umbilical cord blood-derived CD34+ hematopoietic stem cells that are engineered to include two components of the BCMA-CAR and the anti-NKG2D-anti-GPRC5D BsAb. s15.BsAb.BCMA-CAR NK cells can launch dual targeting of both BCMA and GPRC5D antigens expressed on the surface of MM and produce two living agents, CAR NK cells and BsAb, to eradicate MM cells effectively.
Unmet Medical Need
Although BCMA-CAR T cells have been approved by the FDA, MM is still an incurable disease. BCMA-CAR T cells show good response, but most patients eventually relapse. Patients treated with BCMA CAR-T cells experience cytokine release syndrome (CRS) and neurotoxicity.
Project Objective
Complete Pre-IND submission and finalize IND plans
Major Proposed Activities
- Manufacture s15.BsAb.BCMA-CAR NK cells and PK/PD study
- Pharmacology toxicity and optimize treatment schedule of s15.BsAb.BCMA-CAR NK cells in efficacy testing
- Confirm efficacy of s15.BsAb.BCMA-CAR NK cells under optimized and safe conditions and Pre-IND submission
Statement of Benefit to California:
In the United States, the lifetime risk of getting multiple myeloma is 1 in 132 (0.76%). For 2022 in the United States alone, the American Cancer Society's estimates about 34,470 new cases of multiple myeloma will be diagnosed. Blacks may be twice as likely as whites to develop multiple myeloma. Our goal is to develop an “off-the-shelf,” ready-to-use cell therapy that is appropriate and easily accessible for any patient regardless of race, ethnicity, age, or socioeconomic status.