H3.3 CTL Peptides and Uses Thereof

Summary of Invention

PICI investigator Hideho Okada, MD, PhD, at UCSF is developing an adoptive cell therapy to treat diffuse midline glioma (DMG) by targeting a specific mutation that is present in 70 to 80 percent of DMG patients but not in healthy tissues.

Okada identified specific peptides targeting the mutant histone H3.3K27M sequence and T-cell receptors that bind them. Based on these findings, Okada showed that cells expressing this specific TCR could kill cells carrying that mutation in culture. He also replicated these findings in mice using a xenograft model. After showing successful results in vitro and in vivo, PICI and Okada are working together to manufacture a clinical grade T-cell product to treat pediatric DMG patients using a retroviral expression vector.

Potential Impact

Prognosis for pediatric DMG has remained dismal over the last 25 years, and patients with this inoperable, rare cancer have extremely limited treatment options. This adoptive cell therapy has shown promise so far in the laboratory and has the potential to save the lives of children with this deadly cancer. Successfully treating patients with this adoptive cell therapy would be a significant milestone for the immuno-oncology field overall.

Status

PICI is collaborating with Okada on several aspects of this work, including setting up a cell therapy process development lab at UCSF, as well as supporting the next steps for manufacturing the adoptive cell therapy. We are also in the planning stages of a phase 1 clinical trial to test this approach in pediatric patients, primarily to understand potential toxicities, how well the product is tolerated and immune effects of the cells.