Bridges to the Future: 10 Years and Counting!

Bridges conference 2019

When Californians voted for Proposition 71 in 2004, they were investing in hope… the hope that unraveling the mysteries of stem cells could lead to new types of treatments and perhaps one day, even cures for some of the most devastating illnesses and injuries known to mankind. Making this hope a reality, however, requires much more than scientific discovery, it requires a dedicated and skilled work force that can recognize and tackle the challenges that come with such an ambitious dream.

To jump start the nascent stem cell/regenerative medicine community in California, CIRM began offering Training Grants to major research and medical institutions to attract talented PhD students and postdoctoral fellows into the field. A few years later, a second type of training program was born to attract a different, yet equally important cadre of professionals – the undergraduate, Bachelors and Master’s level scientists who are the bread and butter of any successful research endeavor.

Bridges students

Over the past 10 years, CIRM has supported 16 of these programs, which have proven to be among the most popular and successful CIRM initiatives to date. As of 2019, the Bridges programs have trained well over 1400 scientists, about half of whom are working full time in research positions at biotechnology companies or academic laboratories, and another third of whom are currently enrolled in a graduate or professional school.

Today, there are 14 active Bridges Programs around the state, each with unique attributes, but all sharing the core elements of stem cell-based coursework, hands-on-training through internships at world-class laboratories or biotechnology companies, and formal activities involving patient engagement and community outreach. Every year, the programs produce up to 140 well-rounded, highly skilled individuals that are ready to hit the ground running.

Poster presentations at the Bridges conference

Each July, the most recent cohort of Bridges trainees gather for an Annual Conference to share their research outcomes, network with their peers, and learn more about the current opportunities and challenges facing the regenerative medicine community.

This year, the 10th Annual Bridges Conference was held in San Mateo, CA and included inspiring talks from scientists performing cutting edge research and running some of the first FDA-approved stem-cell based clinical trials in the state.

Anna Simos

Perhaps the biggest highlights were hearing the real-life stories of brave individuals like Anna Simos, whose experience with life-threatening complications from diabetes inspired her life’s work of providing hope and education to those facing similar challenges.

Byron Jenkins

Equally moving was the testimonial of Byron Jenkins, a multiple myeloma patient who received an experimental new CAR-T therapy in a CIRM-supported clinical trial sponsored by Poseida Therapeutics.

Ronnie Kashyup with parents Upasana and Pawash

Last but not least, little Ronnie Kashyup, recently cured of Bubble Baby Disease through another CIRM-funded clinical trial, charmed all attendees with his larger-than-life personality while his father, Pawash Priyank, shared the story of Ronnie’s diagnosis and treatment.

In the video segments to follow:

CIRM Bridges student Sneha Santosh at San Jose State University discusses the role CIRM plays in bridging together the patient advocates with the groundbreaking research conducted by scientists.

Samori Dobson and Esther Nair, CIRM Bridges students at California State University, San Marcos, briefly discuss the positive impact that the program has had on their lives.

Below are some pictures form the 10th Annual Bridges Conference in San Mateo, CA.

For more information about CIRM Bridges Programs, see the following link and video below:

CIRM-funded internship programs

Stories that caught our eye: FDA grants orphan drug status to CIRM-funded therapy; stunning discovery upends ideas of cell formation; and how tadpoles grow new tails

Gut busting discovery

Intestinal stem cells: Photo courtesy Klaus Kaestner, Penn Institute for Regenerative Medicine

It’s not often you read the word “sensational” in a news release about stem cells. But this week researchers at the University of Copenhagen released findings that are overturning long-held ideas about the development of cells in our stomachs. So perhaps calling it “sensational” is not too big a stretch.

In the past it was believed that the development of immature cells in our stomachs, before a baby is born, was predetermined, that the cells had some kind of innate sense of what they were going to become and when. Turns out that’s not the case. The researchers say it’s the cells’ environment that determines what they will become and that all cells in the fetus’ gut have the potential to turn into stem cells.

In the “sensational” news release lead author, Kim Jensen, says this finding could help in the development of new therapies.

“We used to believe that a cell’s potential for becoming a stem cell was predetermined, but our new results show that all immature cells have the same probability for becoming stem cells in the fully developed organ. In principle, it is simply a matter of being in the right place at the right time. Here signals from the cells’ surroundings determine their fate. If we are able to identify the signals that are necessary for the immature cell to develop into a stem cell, it will be easier for us to manipulate cells in the wanted direction’.

The study is published in the journal Nature.                             

A tale of a tail

African clawed frog tadpole: Photo courtesy Gary Nafis

It’s long been known that some lizards and other mammals can regrow severed limbs, but it hasn’t been clear how. Now scientists at the University of Cambridge in the UK have figured out what’s going on.

Using single-cell genomics the scientists were able to track which genes are turned on and off at particular times, allowing them to watch what happens inside the tail of the African clawed frog tadpole as it regenerates the damaged limb.

They found that the response was orchestrated by a group of skin cells they called Regeneration-Organizing Cells, or ROCs. Can Aztekin, one of the lead authors of the study in the journal Science, says seeing how ROCs work could lead to new ideas on how to stimulate similar regeneration in other mammals.

“It’s an astonishing process to watch unfold. After tail amputation, ROCs migrate from the body to the wound and secrete a cocktail of growth factors that coordinate the response of tissue precursor cells. These cells then work together to regenerate a tail of the right size, pattern and cell composition.”

Orphan Drug Designation for CIRM-funded therapy

Poseida Therapeutics got some good news recently about their CIRM-funded therapy for multiple myeloma. The US Food and Drug Administration (FDA) granted them orphan drug designation.

Orphan drug designation is given to therapies targeting rare diseases or disorders that affect fewer than 200,000 people in the U.S. It means the company may be eligible for grant funding toward clinical trial costs, tax advantages, FDA user-fee benefits and seven years of market exclusivity in the United States following marketing approval by the FDA.

CIRM’s President and CEO, Dr. Maria Millan, says the company is using a gene-modified cell therapy approach to help people who are not responding to traditional approaches.

“Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

Poseida’s CEO, Eric Ostertag, said the designation is an important milestone for the company therapy which “has demonstrated outstanding potency, with strikingly low rates of toxicity in our phase 1 clinical trial. In fact, the FDA has approved fully outpatient dosing in our Phase 2 trial starting in the second quarter of 2019.”

Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded 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

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, 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