CD8+ T cells

Myocarditis in Cancer Patients Is Driven by Specific Immune Cells

/ Katie Sharify / Leave a comment

In a new study, researchers from UC San Francisco and Vanderbilt University Medical Center have identified specific immune cells that cause a potentially lethal heart inflammation -called myocarditis- in a small fraction of patients treated with powerful cancer immunotherapy drugs.

Myocarditis is inflammation of the heart muscle. It can cause chest pain, shortness of breath, and rapid or irregular heart rhythms. Myocarditis can weaken the heart and its electrical system. As a result, the heart’s ability to pump blood declines. In severe cases, myocarditis causes clots and may lead to stroke, heart attack, heart failure and even death.

The form of myocarditis the researchers studied is a rare but deadly side effect of cancer immunotherapy drugs called immune checkpoint inhibitors (ICIs). 

ICI is a type of therapy method that can improve the anti-tumor immune response by regulating the activity of T cells. ICI treatment has proven lifesaving for many cancer patients and fewer than one percent of patients who receive ICI develop myocarditis.

However, according to Javid Moslehi, MD, chief of Cardio-Oncology and Immunology for the UCSF Heart and Vascular Center, nearly half of patients who do experience ICI-caused myocarditis die as a result. 

Using genetically altered mice to mimic human ICI-caused myocarditis in the new study, the researchers found an excess of immune system cells called CD8 T lymphocytes in the inflamed heart tissue of mice with myocarditis. 

“We earlier observed many T cells in patients who had died, but in the mice we performed several key experiments to show that the T lymphocytes really are drivers of the disease process, and not merely innocent bystanders,” Moslehi said. “There are therapeutic implications to this study.” 

The results of the study led the researchers to conclude that activation of CD8 T cells is necessary to trigger myocarditis in ICI-treated cancer patients and therefore immunosuppressive therapies that affect CD8 T cells might play a beneficial role.

Their new findings already have led them to begin investigating better ways to prevent and treat myocarditis. The research team already has reported a case study in which they used Abatacept, a rheumatoid arthritis drug that suppresses the activation of CD8 T cells, to successfully treat myocarditis in a cancer patient. 

CIRM Board Approves Third Clinical Trial for COVID-19

/ Yimy Villa / Leave a comment
Dr. Xiaokui Zhang (left), Dr. Albert Wong (center), and Dr. Preet Chaudhary (right)

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $750,000 to Dr. Xiaokui Zhang at Celularity to conduct a clinical trial for the treatment of COVID-19.  This brings the total number of CIRM clinical trials to 64, including three targeting the coronavirus.

This trial will use blood stem cells obtained from the placenta to generate natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, and administer them to patients with COVID-19.  NK cells play an important role in defense against cancer and in fighting off viral infections.  The goal is to administer these cells to locate the active sites of COVID-19 infection and destroy the virus-infected cells.  These NK cells have been used in two other clinical trials for acute myeloid leukemia and multiple myeloma.

The Board also approved two additional awards for Discovery Stage Research (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

One award for $100,000 was given to Dr. Albert Wong at Stanford.  Dr. Wong has recently received an award from CIRM to develop a vaccine that produces a CD8+ T cell response to boost the body’s immune response to remove COVID-19 infected cells.  The current award will enable him to expand on the initial approach to increase its potential to impact the Latinx and African American populations, two ethnicities that are disproportionately impacted by the virus in California.

The other award was for $249,996 and was given to Dr. Preet Chaudhary at the University of Southern California.  Dr. Chaudary will use induced pluripotent stem cells (iPSCs) to generate natural killer cells (NK). These NK cells will express a chimeric antigen receptor (CAR), a synthetic receptor that will directly target the immune cells to kill cells infected with the virus.  The ultimate goal is for these iPSC-NK-CAR cells to be used as a treatment for COVID-19. 

“These programs address the role of the body’s immune T and NK cells in combatting viral infection and CIRM is fortunate enough to be able to assist these investigators in applying experience and knowledge gained elsewhere to find targeted treatments for COVID-19” says Dr. Maria T. Millan, the President & CEO of CIRM. “This type of critical thinking reflects the resourcefulness of researchers when evaluating their scientific tool kits.  Projects like these align with CIRM’s track record of supporting research at different stages and for different diseases than the original target.”

The CIRM Board voted to endorse a new initiative to refund the agency and provide it with $5.5 billion to continue its work. The ‘California Stem Cell Research, Treatments and Cures Initiative of 2020 will appear on the November ballot. 

The Board also approved a resolution honoring Ken Burtis, PhD., for his long service on the Board. Dr. Burtis was honored for his almost four decades of service at UC Davis as a student, professor and administrator and for his 11 years on the CIRM Board as both a member and alternate member. In the resolution marking his retirement the Board praised him, saying “his experience, commitment, knowledge, and leadership, contributed greatly to the momentum of discovery and the future therapies which will be the ultimate outcome of the dedicated work of the researchers receiving CIRM funding.”

Jonathan Thomas, the Chair of the Board, said “Ken has been invaluable and I’ve always found him to have tremendous insight. He has served as a great source of advice and inspiration to me and to the ICOC in dealing with all the topics we have had to face.” 

Lauren Miller Rogen thanked Dr. Burtis, saying “I sat next to you at my first meeting and was feeling so extraordinarily overwhelmed and you went out of your way to explain all these big science words to me. You were always a source of help and support, and you explained things to me in a way that I always appreciated with my normal brain.”

Dr. Burtis said it has been a real honor and privilege to be on the Board. “I’ve been amazed and astounded at the passion and dedication that the Board and CIRM staff have brought to this work. Every meeting over the years there has been a moment of drama and then resolution and this Board always manages to reach agreement and serve the people of California.”