Recently, BRL Medicine Inc. (hereinafter referred to as "BRL Medicine")'s new generation of non-viral site-specific integrated CAR-T technology (Quikin CART®) for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphoma (R /R B-NHL) was accepted for publication by eClinicalMedicine , a high-end golden open-access journal which is part of The Lancet Discovery Science that publishes comprehensive medical research .
This is the world's first clinical study of "safety and efficacy of CRISPR-based non-viral PD1 locus specifically integrated anti-CD19 CAR-T cells with relapsed/refractory Non-Hodgkin's lymphoma(pipeline code: BRL-201)". Non-Hodgkin's lymphoma is a hematological malignancy that originates in lymphoid tissue, accounting for 80%-90% of all lymphomas. Although patients get remission after initial treatment, they often relapse afterwards. Although there have been some CAR-T products approved for the clinical treatment of relapsed and refractory non-Hodgkin's lymphoma, the overall efficacy still needs to be improved, and the toxic and side effects caused by the release of a large number of cytokines during the treatment also need to be reduced .
According to the latest clinical data published in the article, a total of 21 patients were enrolled, including 19 patients (90%) who were diagnosed as stage III or IV, with moderate or more serious disease risk; The expression rate of PD-L1 in tumor tissue is greater than 50%. The results showed that even though the patient's expected prognosis was poor, the treatment with the non-viral PD1-CAR-T cell product BRL-201 still achieved satisfactory curative effect. The patient's objective response rate (ORR) was as high as 100% , and the complete remission rate ( CR) reached 85.7% . While achieving significant curative effect, it did not cause cytokine release syndrome or neurotoxicity above grade 2 in any patient; and the median progression-free survival (mPFS) reached 19.5 months, and the long-term benefit of patients was significantly higher than the current one . There are similar virus CAR-T products. This study proves the excellent clinical safety and efficacy of BRL-201, and it is the best clinical result so far in the global CAR-T cell therapy of refractory relapsed lymphoma with high remission rate and low toxicity. It is worth mentioning that the multi-center phase I/II registration clinical study of BRL-201 has now been officially launched.
About BRL-201: Safer, More Effective, More Accessible
BRL-201, indicated for relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL), is a CAR-T product derived from the non-viral site-specific integrated CAR-T platform (Quikin CART®) independently developed by BRL Medicine. BRL-201 is also the world's first CAR-T product targeting CD19 non-viral PD1 site-specific integration. On December 14, 2022, it was approved by China's IND and officially entered the registration clinical stage.
1) Low cost, can benefit more patients
BRL-201 uses the 2020 Nobel Prize-winning CRISPR/Cas9 gene editing technology to precisely edit the PD1 site in T lymphocytes without the use of viral vectors, and inserts CAR molecules targeting CD19 targeting tumor cells at specific sites. The use of non-viral production processes can greatly reduce the high cost caused by the use of viral vectors and reduce complex production processes.
2) Fast preparation, suitable for patients with rapid progress
From the perspective of production process, the preparation time of traditional CAR-T products is relatively long, which greatly increases the time for patients to wait for medication, and also means that such CAR-T products cannot be used for patients with very fast tumor progression. The BRL-201 product of BRL Medicine adopts a non-viral preparation method, and the process is simple. It only needs one-step preparation to realize the continuous expression of CAR and the regulation of endogenous genes in T cells at the same time, which greatly shortens the preparation of the entire CAR-T The preparation time can be completed in as little as 3 days, which greatly improves the production capacity and can be used in the treatment of patients with fast tumor progression in time.
3) Safer and ensure the uniformity of the product
Non-viral site-specific integration allows each CAR sequence to be precisely inserted into a specific site in the genome, avoiding the risk of tumorigenesis caused by random insertion, and ensuring the safety and effectiveness of CAR-T products to the greatest extent. In the IIT clinical trial of BRL-201 in the treatment of relapsed/refractory non-Hodgkin's lymphoma , after 21 patients received treatment, no CAR-T treatment-related neurotoxicity and cytokine storm above grade 2 were observed. It proved that BRL-201 has excellent clinical safety.
4) More effective, breaking the shackles of relapse and refractory treatment
The clinical research results of BRL-201 have proved that the product has excellent clinical effectiveness, and is by far the best clinical result of high remission rate and low side effects in the treatment of refractory relapsed lymphoma in the world by CAR-T cells, and patients have long-term benefit. The benefit is significantly higher than that of existing similar virus CAR-T products, and mPFS has increased from 2.9-12.8 months (existing virus CAR-T) to 20 months (BRL-201 CAR-T). The results of single-cell sequencing showed that the BRL-201 cell product has a high proportion of memory T cells and has a stronger anti-tumor immune function, and the CAR-T cells after reinfusion have the ability to persist for a long time.