DopineFebruary 26, 2018
Tag: CDE , CAR-T , Unicar , OCTS-CAR-T
2017 was an important node in the development of CAR T-cell immunotherapy, where the two cell immunotherapies of Novartis and Gilead were successively approved by FDA. The CAR-T development in China has received attention since Nanjing Legend Biotechnology stunned in 2017 ASCO annual meeting. There have been 7 companies including Nanjing Legend Biotechnology filing clinical trial applications to CDE, wherein, Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd. (Unicar) is different from the rest, with indication and CAR-T product design being the bright spots.
I. Unicar different from the rest: the indication is central nervous system (CNS) leukemia
According to the public data, 2 CAR T-cell immunotherapies of Shanghai Unicar were accepted by CDE on January 31, 2018, with the information as follows: 1. CXSL1800005, IL-6 secretion function knocking down, CD19-targeted autologous gene editing T-cell injection; 2. CXSL1800006, IL-6 secretion function knocking down, CD19-targeted autologous gene editing T-cell injection, with indications of CNS leukemia (CD19+) and acute B-lymphoblastic leukemia (CD19+). The CNS leukemia is included in the indications applied for by Unicar this time, which is a quite noteworthy point.
We know that the CNS leukemia often occurs in the remission of the acute lymphoblastic leukemia, leading to the CNS reactions of patients, which is considered as an important reason for the disease recurrence of patients. The conventional CAR-T has three safety issues: 1. CRS (cytokine release syndrome), how to solve this issue has been a subject of concern; 2. Product central neurotoxicity; 3. Off-target effect. Given the CNS safety concerns of the conventional CAR-T, CNS leukemia patients often cannot be enrolled, and there is rarely the CAR-T product for this indication at present.
Unicar is different: the company has designed the new-generation CAR T-cell product with much improved safety based on the unique OCTS-CAR-T technology. According to part of the clinical data made public by the company, the products’ severe CRS (above class III) is 15.5%, and severe central neurotoxicity is 5.4%, which are lower than similar products. A part of the data is as follows:
Disease |
Refractory and relapsed acute B-lymphoblastic leukemia |
|||||
Company |
Juno |
Kite |
Novartis |
Unicar |
||
Number of cases |
24 |
11 |
55 |
29 |
68 |
129 |
Product |
JCAR-014 |
Yescarta |
Tisagenlecleucel |
SssUCA-019 |
||
Complete response (CR) |
88% |
82% |
94.5% |
69% |
82.5% |
85.5% |
Severe CRS (above class III) |
35.6% |
46% |
N/A |
N/A |
63.20% |
15.5% |
Severe central neurotoxicity |
28% |
22% |
N/A |
N/A |
1 death |
5.4% |
CR above 6 months |
50% |
56% |
N/A |
N/A |
79% |
54.5% |
Data extracted from Unicar website
And the new-generation CAR-T product designed by Unicar based on OCTS-CAR-T technology had the case of successfully treating CNS leukemia. Unicar’s product has great advantages in terms of safety, which is noteworthy.
II. Unicar different from the rest: analysis of OCTS-CAR-T technology
Data extracted from Unicar
The CAR-T technology has gradually become mature after 4 generations (as shown in the figure), and how to solve the safety concerns is what the new-generation CAR-T products shall focus on. Unicar has found a new path with the unique OCTS-CAR-T, which greatly improves the safety of the CAR-T product.
OCTS-CAR-T, namely, One CAR with Two ScFvs, integrates two scFvs into one chimeric molecule via series OCTS or turn OCTS, to give T cells the ability to identify two tumor antigens, which can identify broader targets than the conventional CAR T cells, to further expand the tumor cell clearance range, being a feature of Unicar.
Specific to this product, Unicar constructed the lentiviral vector skeleton, OCTS domain, interleukin-6 receptor (IL6R)’s single-chain antibody to form the recombinant lentiviral vector which can express the IL-6R’s single-chain antibody in human T cells to block IL-6 signaling pathway, and can be clinically used to relieve the Cytokine Release Syndrome (CRS) and guarantee patients’ life safety during cell therapy process. (Extracted from the patent CN 107245500 A)
To sum up, Unicar’s product has the following characteristics: 1. Optimizing the lentiviral transfection system; 2. Dual CAR design based on OCTS technology; 3. Tumor inhibition and immune escape avoidance, such as the CAR T cell transformation technology with the attempt to knock down PD-1; 4. Technological exploration in reducing CRS, such as the design to block IL-6 signaling pathway.
Currently, the two PD-1 knocking down CAR T-cell products of the company are also being applied for clinical trials.
Attached:
Some patents of the multiple patents applied for by Unicar for its OCTS-CAR-T technology are as follows:
Some patents |
Unicar |
CN107177632 A |
Myeloid leukemia CAR-T treatment carrier based on OCTS technology and construction method and application of myeloid leukemia CAR-T treatment carrier |
CN107299110 A |
Pancreatic cancer and malignant mesothelioma CAR-T treatment carrier based on OCTS technology and construction method and application thereof |
CN107164410 A |
OCTS technology-based prostatic cancer CAR-T therapy vector and construction method and application thereof |
CN107287207 A |
Tag used for in vivo tracking and CAR T cell manual clearance and application thereof |
CN 107325185 A |
OCTS-CAR-based anti-PCSA and PDL1 chimeric antigen receptor, coding gene, and expression vector |
CN 107267555 A |
Glioblastoma CAR-T treatment carrier based on OCTS technology and construction method and application thereof |
CN 107245500 A |
Lymphoblastic leukemia CAR-T treatment carrier based on OCTS technology and construction method and application thereof |
CN 107337736 A |
OCTS-CAR dual targeting chimeric antigen receptor, coding gene, and recombinant expression vector and construction method and application thereof |
CN 107058232 A |
CAR-T cells with inhibited sterol o-acyltransferase 1 (SOAT1) as well as preparation method and application of CAR-T (Chimeric Antigen Receptor-T-cell Immunotherapy) cells |
CN 107058315 A |
SiRNA capable of knocking down human PD-1, recombinant expression CAR-T vector as well as construction method and application thereof |
Unicar product pipeline:
References: unicar-therapy
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