Educational content on VJHemOnc is intended for healthcare professionals only. By visiting this website and accessing this information you confirm that you are a healthcare professional.

Share this video  

EHA 2021 | CD19/CD20 dual STAR T-cell therapy for R/R B-ALL

Peihua Lu, MD, Lu Daopei Hospital, Langfang, China and Lu Daopei Institute of Hematology, Beijing, China, talks on preclinical and Phase I data (NCT04260945) on a novel CD19/CD20 dual synthetic T-cell receptor and antigen receptor (STAR) T-cell therapy (STAR-T) for patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Dr Lu gives an overview of the mechanism of action of STAR, and discusses recent data. Dr Lu reports that 8/9 patients who received dual STAR-T therapy achieved a complete remission with measurable residual disease (MRD)-negativity, and gives an overview of the safety profile of STAR-T therapy. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.

Transcript (edited for clarity)

As you all know, CAR-T therapy has been very successful for treating hematological malignancy. However, it’s the safety and the duration of remission, the cure rate, still need to have further improvement. So, we have developed a TCR complex-based CAR, called the synthetic TCR and antigen receptor, we named STAR. STAR consists of two protein modules, each containing an antibody light or heavy chain variable region and the T-cell receptor, alpha or beta constant region, then fused to the OX-40 co-stimulated domain...

As you all know, CAR-T therapy has been very successful for treating hematological malignancy. However, it’s the safety and the duration of remission, the cure rate, still need to have further improvement. So, we have developed a TCR complex-based CAR, called the synthetic TCR and antigen receptor, we named STAR. STAR consists of two protein modules, each containing an antibody light or heavy chain variable region and the T-cell receptor, alpha or beta constant region, then fused to the OX-40 co-stimulated domain.

So, with this new structure, actually this structure is somewhat between a CAR-T and a TCR-T. So, we previously reported this high successful clinical efficacy and safety with the CD19 single target STAR-T for treatment of refractory/relapsed B-ALL. We reported in ASH Meeting in the last year. So, based on this success, we now, we further, we developed this into a dual CAR, dual CAR-T target anti-CD19 and CD20 for treating refractory/relapsed B-cell ALL.

So, previously, we said single CD19 target, 20 out of the 20 patients able to achieve MRD-negative complete remission, just in 14 days after this STAR-T infusion. And this time, again, we infused this dual CAR-T for patient. Eight out of nine patients able to achieve complete remission, which is MRD-negative complete remission on day 14.

With this high success, actually it’s quite a safe product. The majority of patients only have a mild cytokine release syndrome, some of patient without even have any side effects, really have any grade III toxicity and also have very minimal, very mild neurotoxicity. So, we see this potential, this new structure potential have it’s broader application because this is a TCR-based structure. So, we can see in the future, more potential for its application for solid tumor and we already in animal model, we already proved in animal model show very promising results and we currently also doing the clinical trial for solid tumor.

Nevertheless, this is just to prove the concept, it’s clinical feasible, and we able to do manufacture almost 100% success and show the high efficacy and the low toxicity, so we’re very happy about these results.

Read more...