Dr. Yvonne Chen

CIRM Board Awards $15.8 Million to Four Translational Research Projects

/ Yimy Villa / Leave a comment

Last week, the CIRM Board approved $32.92 million in awards directed towards four new clinical trials in vision related diseases and Parkinson’s Disease.

In addition to these awards, the Board also approved investing $15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Before we go into more specific details of each one of these awards, here is a table summarizing these four new projects:

ApplicationTitleInstitutionAward Amount
TRAN1 11536Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper IgM Syndrome  UCLA $4,896,628
TRAN1 11555BCMA/CS1 Bispecific CAR-T Cell Therapy to Prevent Antigen Escape in Multiple Myeloma  UCLA $3,176,805
TRAN1 11544 Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer  City of Hope $2,873,262
TRAN1 11611Development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsyNeurona Therapeutics$4,848,750
Dr. Caroline Kuo, UCLA

$4.89 million was awarded to Dr. Caroline Kuo at UCLA to pursue a gene therapy approach for X-Linked Hyper IgM Syndrome (X-HIM).

X-HIM is a hereditary immune disorder observed predominantly in males in which there are abnormal levels of different types of antibodies in the body.  Antibodies are also known as Immunoglobulin (Ig) and they combat infections by attaching to germs and other foreign substances, marking them for destruction.  In infants with X-HIM, there are normal or high levels of antibody IgM but low levels of antibodies IgG, IgA, and IgE.  The low level of these antibodies make it difficult to fight off infection, resulting in frequent pneumonia, sinus infections, ear infections, and parasitic infections.  Additionally, these infants have an increased risk of cancerous growths. 

The gene therapy approach Dr. Kuo is continuing to develop involves using CRISPR/Cas9 technology to modify human blood stem cells with a functional version of the gene necessary for normal levels of antibody production.  The ultimate goal would be to take a patient’s own blood stem cells, modify them with the corrected gene, and reintroduce them back into the patient.

CIRM has previously funded Dr. Kuo’s earlier work related to developing this gene therapy approach for XHIM.

Dr. Yvonne Chen, UCLA

$3.17 million was awarded to Dr. Yvonne Chen at UCLA to develop a CAR-T cell therapy for multiple myeloma (MM).

MM is a type of blood cancer that forms in the plasma cell, a type of white blood cell that is found in the bone marrow.  An estimated 32,110 people in the United States will be diagnosed with MM in 2019 alone.  Several treatment options are available to patients with MM, but there is no curative therapy.

The therapy that Dr. Chen is developing will consist of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called a chimeric antigen receptor (CAR) that will recognize BCMA and CS1, two different markers found on the surface of MM cells.  These modified T cells (CAR-T cells) are then infused into the patient, where they are expected to detect and destroy BCMA and CS1 expressing MM cells.

Dr. Chen is using CAR-T cells that can detect two different markers in a separate clinical trial that you can read about in a previous blog post.

Dr. Karen Aboody, City of Hope

$2.87 million was awarded to Dr. Karen Aboody at City of Hope to develop an immunotherapy delivered via neural stem cells (NSCs) for treatment of ovarian cancer.

Ovarian cancer affects approximately 22,000 women per year in the United States alone.  Most ovarian cancer patients eventually develop resistance to chemotherapy, leading to cancer progression and death, highlighting the need for treatment of recurring ovarian cancer.

The therapy that Dr. Aboody is developing will use an established line of NSCs to deliver a virus that specifically targets these tumor cells.  Once the virus has entered the tumor cell, it will continuously replicate until the cell is destroyed.  The additional copies of the virus will then go on to target neighboring tumor cells.  This process could potentially stimulate the body’s own immune response to fight off the cancer cells as well.

Dr. Cory Nicholas, Neurona Therapeutics

$4.85 million was awarded to Dr. Cory Nicholas at Neurona Therapeutics to develop a treatment for epilepsy.

Epilepsy affects more than 3 million people in the United States with about 150,000 newly diagnosed cases in the US every year. It results in persistent, difficult to manage, or uncontrollable seizures that can be disabling and significantly impair quality of life. Unfortunately, anti-epileptic drugs fail to manage the disease in a large portion of people with epilepsy. Approximately one-third of epilepsy patients are considered to be drug-resistant, meaning that they do not adequately respond to at least two anti-epileptic drugs.

The therapy that Dr. Nicholas is developing will derive interneurons from human embryonic stem cells (hESCs). These newly derived interneurons would then be delivered to the brain via injection whereby the new cells are able to help regulate aberrant brain activity and potentially eliminate or significantly reduce the occurrence of seizures.

CIRM has previously funded the early stage development of this approach via a comprehensive grant and discovery grant.

UCLA Conducts CAR-T Cell Clinical Trial for Patients with Recurring and Non-Responsive Cancers

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Dr. Sarah Larson (left) and Dr. Yvonne Chen (right)

There have been many advances made towards the treatment of various cancers, such as deadly forms of leukemia and lymphoma, that were once considered a death sentence and thought to be incurable. Unfortunately, there are still people who do not respond to treatment or eventually relapse and see the cancer return. However, researchers at UCLA are attempting to fine-tune some of these approaches to help people with these recurring and non-treatment responding cancers.

Diagram describing CAR-T cell therapy

Dr. Sarah Larson and Dr. Yvonne Chen at UCLA are conducting a clinical trial that involves genetically-modifying a patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells. The T-cells are modified with a protein called a chimeric antigen receptor (CAR), which identifies and destroys the cancer by detecting a specific protein, referred to as an antigen, on the cancer cells. These genetically modified T-cells are referred to as CAR-T cells and are re-introduced back into the patient as part of the therapy.

Previous CAR-T cells developed can only recognize one specific protein. For example, one FDA-approved CAR-T cell therapy is able to recognize a protein called CD19, which is found in B-cell lymphoma and leukemia. However, over time, the cancer cells can lose the CD19 antigen, making the CAR-T cell ineffective and can result in a reoccurrence of the cancer.

In a news release by UCLA, Dr. Larson describes the limitations of this design:

“One of the reasons CAR T cell therapy can stop working in patients is because the cancer cells escape from therapy by losing the antigen CD19, which is what the CAR T cells are engineered to target.”

But Dr. Larson and Dr. Chen are using a CAR-T cell that is able to recognize not one by two proteins simultaneously. In addition to recognizing CD19, their CAR-T cell is also able to recognize a protein called CD20, which is also found in B-cell lymphoma and leukemia. This is called a bispecific CAR-T cell because of it’s ability to identify two protein targets simultaneously.

In the same UCLA news release, Dr. Larson hopes that this approach will be more effective:

“One way to keep the CAR T cells working is to have more than one antigen to target. So by using both CD19 and CD20, the thought is that it will be more effective and prevent the loss of the antigen, which is known as antigen escape, one of the common mechanisms of resistance.”

Before the clinical trial, Dr. Chen and her team at UCLA conducted preclinical studies that showed how using bispecific CAR-T cells provided a much better defense compared to single target CAR-T cells against tumors in mice.

In the same UCLA news release, Dr. Chen elaborate on the results of her preclinical studies:

“Based on these results, we’re quite optimistic that the bispecific CAR can achieve therapeutic improvement over the single-input CD19 CAR that’s currently available.”

This first-in-humans study will evaluate the therapy in patients with non-Hodgkin’s B-cell lymphoma or chronic lymphocytic leukemia that has come back or has not responded to treatment. The goal is to determine a safe therapeutic dose.