Every year, California performs around 100 kidney transplants in children, but, on average, around 50 of these patients will have their bodies reject the transplant.
Improving kidney transplant outcomes
These children then have to undergo regular dialysis while waiting for a new organ. Even the successful transplants require a lifetime of immunosuppression medications. These medications can prevent rejection, but they also increase the risk of infection, gastrointestinal disease, pancreatitis, and cancer.
Dr. Alice Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that combines blood stem cell (HSC) and kidney transplantation to improve outcomes in children. This approach aims to improve blood stem cell preparation through an immune-based purification process.
Averting rejection
In this approach, donor HSCs are transplanted into the patient to prepare for acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney providing the opportunity to avoid long-term need for medications that suppress the immune system.
Pre-clinical data support the idea that this approach could enable patients to stop taking immunosuppression medications within 90 days of surgery.
Dr. Maria T. Millan, President and CEO of CIRM, a former pediatric transplant surgeon and tolerance researcher, states that “developing a way to ensure long-term success of organ transplantation by averting immune rejection while avoiding the side effects of life-long immunosuppression medications would greatly benefit these children.”
Blocking tumors
The CIRM Board also awarded $7,141,843 to Dr. Ivan King and Tachyon Therapeutics, Inc. to test a drug showing promise in blocking the proliferation of cancer stem cells in solid tumors such as colorectal and gastrointestinal cancer.
Patients with late-stage colorectal cancer are typically given chemotherapy to help stop or slow down the progression of the disease. However, even with this intervention, survival rates are low, usually not more than two years.
Tachyon’s medication, TACH101, is intended to target colorectal cancer (CRC) stem cells and the bulk tumor by blocking an enzyme called KDM4, which cancer stem cells need to grow and proliferate.
In the first phase of this trial, Dr. King and his team will recruit patients with advanced or metastatic solid tumors to assess the safety of TACH101 and determine the safest maximum dose. In the second phase of the trial, patients with gastrointestinal tumors and colorectal cancer will be treated using the dose determined in the first phase, to determine how well the tumors respond to treatment.
Hurler syndrome
The CIRM Board also awarded $5,999,919 to Dr. Natalia Gomez-Ospina and her team at Stanford University for a late-stage preclinical program targeting Severe Mucopolysaccharidosis type 1, also known as Hurler syndrome. This inherited condition is caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs. There is no effective treatment, and life expectancy for many of these children is only around ten years.
Dr. Gomez-Ospina will use the patient’s own blood stem cells, genetically edited to restore the missing enzyme. The goal of this preclinical program is to show the team can manufacture the needed cells, to complete safety studies, and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.
Finally, the Board awarded $20,401,260 to five programs through its Translational program. The Translational program supports promising stem cell-based or gene projects that accelerate completion of translational-stage activities necessary to advance to clinical study or broad end use. Those can include therapeutic candidates, diagnostic methods or devices, and novel tools that address critical bottlenecks in research.
Awards
| APPLICATION | TITLE | PRINCIPAL INVESTIGATOR – INSTITUTION | AMOUNT |
| TRAN4-14124 | Cell Villages and Clinical Trial in a Dish with Pooled iPSC-CMs for Drug Discovery | Nikesh Kotecha — Greenstone Biosciences | $1,350,000 |
| TRAN1-14003 | Specific Targeting Hypoxia Metastatic Breast Tumor with Allogeneic Off-the-Shelf Anti-EGFR CAR NK Cells Expressing an ODD domain of HIF-1α | Jianhua Yu — Beckman Research Institute of City of Hope | $6,036,002 |
| TRAN1-13983 | CRISPR/Cas9-mediated gene editing of Hematopoietic stem and progenitor cells for Friedreich’s ataxia | Stephanie Cherqui — University of California, San Diego | $4,846,579 |
| TRAN1-13997 | Development of a Gene Therapy for the Treatment of Pitt Hopkins Syndrome (PHS) – Translating from Animal Proof of Concept to Support Pre-IND Meeting | Allyson Berent — Mahzi Therapeutics | $4,000,000 |
| TRAN1-13996 | Overcoming resistance to standard CD19-targeted CAR T using a novel triple antigen targeted vector | William J Murphy — University of California, Davis | $4,168,679 |