After being diagnosed with diffuse large B-cell lymphoma more than four years ago, Mr. Sun underwent a long and painful regimen that included 14 rounds of chemotherapy with various regimens, 20 rounds of radiation, and a total gastrectomy. have been treated with However, the efficacy was not satisfactory as the tumor recurred repeatedly.

“Fate had already sentenced me to death, and I saw no hope.”

In May 2020, Mr. Sun was transferred to the First Affiliated Hospital of Zhejiang University School of Medicine (FAHZU). After preliminary evaluation, he received his new PD1-19bbz CAR-T cell therapy. As a result, Mr. Sun has been disease-free for over two years.

“Thank you to the new CAR-T therapy for giving me a second life!”

This is the best clinical result to date in global CAR-T cell therapy for refractory and relapsed lymphoma with high remission rate and low toxicity, and marks the beginning of CAR-T cell research and development by Chinese scientists. It represents an international leading position in the field. and clinical translation.

On August 31, 2022, FAHZU’s Professor HUANG He’s team, in collaboration with East China Normal University’s Professor LIU Mingyao, announced that “non-viral, specifically targeted CAR-T cells are highly safe in B cells. and Achieving Effectiveness,” published a research article. -Nature online. His Dr. ZHANG Jiqin of Professor Liu’s team and his Dr. HU Yongxian of his FAHZU are co-first authors.

Together, the two teams used CRISPR/Cas9, a gene-editing technology that won the Nobel Prize in 2020, to precisely knockout the PD1 locus in T lymphocytes and to insert the anti-CD19 CAR cassette into the AAVS1 safe harbor. inserted into the locus. Development of an innovative anti-CD19 CAR-T cell (PD1-19bbz) that integrates PD1.

In 2020, when Mr. Sun first came to FAHZU, he had multiple lymphoma lesions in his abdominal cavity and the lymphoma had invaded the intestinal wall. Huang’s team’s research shows that lymphoma that invades the intestinal wall is a relative contraindication to CAR-T therapy, and intestinal perforation is more likely to occur with CAR-T cell therapy. Therefore, Mr. Sun is no longer suitable for his traditional CAR-T cell therapy. The new Her PD1-19bbz CAR-T cells may give patients a chance at survival with a lower risk of cytokine storm and other complications.

After completing various clinical trial approvals, Professor Huang’s team infused the patient with PD1-19bbz CAR-T cells on May 26, 2020. After 14 days from re-injection he was normal on June 9th. After evaluation, the patient was discharged. A PET-CT evaluation was performed one month after her re-implantation. As a result, the large-mass tumor that had invaded the original intraperitoneal intestinal mucosa had completely disappeared. Sun has also confirmed that he has been disease-free for over two years.

Left: before CAR-T therapy.Right: 1 month after CAR-T treatment

In the most recent study, mild cytokine release syndrome (CRS) was observed in some patients, but immune effector cell-associated neurotoxic syndrome (ICANS) did not occur. No other high-grade (≥3) adverse events (AEs) were found for all patients who experienced transient and reversible hematologic toxic events primarily related to chemotherapy prior treatment. And these data demonstrate that non-viral, PD1-integrated CAR-T cells have high safety and efficacy in patients with r/r B-NHL.

Figure. Non-viral, PD1-integrated CAR-T cells potently eliminate tumor cells from r/r B-NHL patients without severe toxicity.

A recent follow-up found that Mr. Sun passed the criteria on all tests. His weight has increased significantly and his face looks more rosy. In the summer of 2022, Mr. SUN gave the medical staff the wonderful news that his son had entered the Tsinghua University College of Art and Design. After cell therapy, my body quickly returned to normal. My relatives and friends also learned that I had miraculously recovered. Thanks to his new CAR-T cell therapy, he can now see his son go to college. Thanks to the meticulous treatment of Professor HUANG He’s team, I was able to overcome my illness and feel alive again.

Source: Zhejiang University First Affiliated Hospital