About Dr. Ramakrishna
Sneha Ramakrishna obtained her B. A. from the University of Chicago and her M.D. from the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. In medical school, through the Howard Hughes Medical Research Scholar Award, she joined Dr. Crystal Mackall’s laboratory, where she designed and developed various GD2 CAR-Ts and tested them in preclinical models. During her residency training in Pediatrics at the Children’s Hospital of Philadelphia, she cared for some of the first patients treated with CD19 CAR T cells, learning the power of this therapy first-hand. During her fellowship in Pediatric Hematology/Oncology at the Johns Hopkins/National Cancer Institute combined program, she worked with Dr. Terry Fry. She evaluated the mechanism of CD22 CAR T cell relapse in patients by developing an antigen escape model and establishing a deeper understanding of the effects of antigen density on CAR-T phenotype, expansion, and persistence. Since arriving at Stanford, Dr. Ramakrishna leads an interdisciplinary team that designs, develops, and successfully implements a robust correlative science platform for CAR-T therapies.
2023 ChadTough Defeat DIPG New Investigator Grant
Over the past decade, children with certain types of cancer have been successfully treated with a new therapy called chimeric antigen receptor T cells (CAR T-cells). CAR T-cells work by teaching the immune system, specifically the T cells, to find and kill cancer cells. However, until recently CAR T-cells were unavailable in children with brain tumors. In 2021, Stanford doctors, including Dr. Ramakrishna, opened a clinical trial to use CAR T-cells to treat children and young adults with diffuse intrinsic pontine glioma (DIPG), a universally fatal tumor of the brain. Excitingly, 10 out of 12 subjects infused with these CAR T-cells have responded with tumors shrinking and improvement in their symptoms. Unfortunately, not all patients respond to the treatment and it is now known that, at least for some patients, the tumor can resist the treatment.
In 2023, Dr. Ramakrishna was awarded a ChadTough Defeat DIPG New Investigator grant to explore the resistance of CAR T-cell therapy in DIPG patients.
Initial Findings
Dr. Ramakrishna’s project titled Immune Determinants of GD2 CAR-T Cell Activity in Patients with DIPG seeks to learn from patients to understand why CAR T-cells succeed or fail, with the goal of identifying approaches to improve this treatment for patients. To do so, she developed a comprehensive platform to collect patient samples throughout CAR T-cell treatment.
Dr. Ramakrishna and her team studied samples from patients in the first-in-human GD2 CAR-T trial treating DIPG. They discovered that when the CAR-T cells were delivered directly into the brain, there was a stronger immune response and fewer cells that suppress the immune system, compared to when the treatment was given through the bloodstream. Now, her team is using advanced techniques to analyze individual cells from patients to better understand what makes the treatment work or fail. Based on what they’ve learned, they’re exploring ways to improve the effectiveness of CAR-T therapy and bring these improvements to the clinic.
The 2023 ChadTough Defeat DIPG New Investigator grant is allowing Dr. Ramakrishna and her team to learn how to improve CAR T-cell therapy for DIPG patients with the ultimate goal to cure this incurable disease.