Stem cell agency invests in therapy using killer cells to target colorectal, breast and ovarian cancers

While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.

BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.

This is the 78th clinical trial funded directly by the Stem Cell Agency.

BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”

They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.

“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.  

The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.

The awards went to:

ApplicationTitleInstitutionAward Amount
TRAN1-133442Optogenetic therapy for treating retinitis pigmentosa and
other inherited retinal diseases  
  Paul Bresge Ray Therapeutics Inc.  $3,999,553  
TRAN3-13332Living Synthetic Vascular Grafts with Renewable Endothelium    Aijun Wang UC Davis  $3,112,567    
TRAN1-13370Next generation affinity-tuned CAR for prostate cancer    Preet Chaudhary University of Southern California  $5,805,144  
TRAN1-3345Autologous MPO Knock-Out Hematopoietic Stem and
Progenitor Cells for Pulmonary Arterial Hypertension  
  Don Kohn UC Los Angeles  $5,207,434  

Improving a special kind of cell to help combat immune related problems

Regulatory T cells (Tregs) are a type of immune cell that play an extremely important role in maintaining stability in the body and preventing the body’s immune system from attacking its own cells and organs. This unique property makes Tregs extremely valuable to researchers as a potential treatment for immune related issues. One of these is autoimmune disease, which is a disease in which the body’s own immune system attacks healthy cells. Some examples of this are type 1 diabetes, multiple sclerosis, and lupus. Another immune related issue is graft vs. host disease (GvHD), which can occur after receiving a transplantation where the donated bone marrow or stem cells start attacking the recipient.

For this reason, researchers at the La Jolla Institute for Immunology (LJI) and Emory University School of Medicine, partially supported by a CIRM training grant , have been working to generate stable induced Tregs (iTregs) for treating autoimmune diseases and rejection of a transplanted organ. The teams were led by LJI professor Anjana Rao, Ph.D, and Emory instructor Benjamin G. Barwick, Ph.D. The two team study showed evidence that vitamin C and and specific proteins called TET can be combined to give Tregs their life-saving power. Studies have previously found that vitamin C can enhance the activity of TET proteins and prompt the generation of stable iTregs under lab conditions.

For this study, the researchers also analyzed gene expression patterns as well as changes that altered the physical structure of DNA in the induced Tregs. The team found a major modification involving the DNA itself and showed that TET enzymes were also involved. All of these interactions can eventually change how cells “read” the DNA code. They also observed the alteration of DNA accessibility which depends on whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression.

In a news release, LJI instructor Xiaojing Yue, Ph.D elaborated on the results of this study.

“Vitamin C can be used to stabilize iTregs generated in vitro. We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation.”

The full study was published in EMBO reports.