A program hoping to supercharge prostate cancer research by using a patient’s own immune system cells received $3.99 million from the California Institute for Regenerative Medicine (CIRM)

A leading cause of death

Prostate cancer is the second‑leading cause of cancer deaths in U.S. men. Each year, about 170,000 men are diagnosed, and more than 29,000 are expected to die from the disease. Early‑stage prostate cancer is often treated with surgery, radiation, and hormone therapy, but for men with castrate‑resistant metastatic prostate cancer (CRPC), these options usually fail, and the disease becomes fatal.

A New CAR‑T Approach for Metastatic CRPC

CIRM is funding Poseida Therapeutics to develop genetically engineered chimeric antigen receptor T cells (CAR‑T) to treat metastatic CRPC. In cancer, the immune system loses its ability to detect and destroy malignant cells. Poseida is engineering T cells—and T memory stem cells—to express a CAR that helps them recognize, bind to, and kill cancer cells more effectively. After being engineered and expanded in the lab, millions of these cells are re‑infused into the patient. The modified T memory stem cells may persist long‑term and eliminate remaining cancer cells.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “CAR‑T therapies have shown impressive results in blood cancers, and extending this approach to solid tumors like metastatic prostate cancer is a natural next step. CIRM is pleased to partner on this program and add it to its CAR‑T memory stem cell portfolio.”

Poseida will use the funding to complete the late‑stage studies needed to apply to the FDA to begin a clinical trial.

New Discovery Awards to Advance Stem Cell Science

The CIRM Board also approved $10 million for eight new projects under the Discovery Quest Program, which supports early‑stage stem cell technologies expected to advance to the translational stage within two years.

Projects funded include:

• Eric Adler, UC San Diego – using genetically modified blood stem cells to treat Danon Disease, a rare and fatal heart condition
• Li Gan, Gladstone Institutes – using induced pluripotent stem cells to develop a therapy for a familial form of dementia
• Saul Priceman, City of Hope – developing a CAR‑T therapy for recurrent ovarian cancer

Because the recommended applications exceeded the available funds, the Application Subcommittee approved partial funding for two projects (DISC2‑11192 and DISC2‑11109) and will recommend that the remainder be approved at the next full Board meeting in October.

CAR-T approach

The successful applications are led by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

• Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
• Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
• Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

The amount of funding for the recommended applications exceeded the money set aside. Because of that the Application Subcommittee voted to approve partial funding for two projects. Those two were DISC2-11192 and DISC2-11109. The board also ecommended that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

APPLICATION	TITLE	INSTITUTION	CIRM COMMITTED FUNDING
DISC2-11131	Genetically Modified Hematopoietic Stem Cells for the Treatment of Danon Disease	U.C San Diego	$1,393,200
DISC2-11157	Preclinical Development of An HSC-Engineered Off- The-Shelf iNKT Cell Therapy for Cancer	U.C. Los Angeles	$1,404,000
DISC2-11036	Non-viral reprogramming of the endogenous TCRα locus to direct stem memory T cells against shared neoantigens in malignant gliomas	U.C. San Francisco	$900,000
DISC2-11175	Therapeutic immune tolerant human islet-like organoids (HILOs) for Type 1 Diabetes	Salk Institute	$1,637,209
DISC2-11107	Chimeric Antigen Receptor-Engineered Stem/Memory T Cells for the Treatment of Recurrent Ovarian Cancer	City of Hope	$1,381,104
DISC2-11165	Develop iPSC-derived microglia to treat progranulin- deficient Frontotemporal Dementia	Gladstone Institutes	$1,553,923
DISC2-11192	Mesenchymal stem cell extracellular vesicles as therapy for pulmonary fibrosis	U.C. San Diego	$865,282
DISC2-11109	Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome	Stanford University	$865,282