September 25, 2022

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CAR-T therapy by Nobel Prize team: The total remission rate is 100%

CAR-T therapy by Nobel Prize team: The total remission rate is 100%



 

CAR-T therapy by Nobel Prize team: The total remission rate is 100%.

The total remission rate is 100%: The  CAR-T therapy developed by the Nobel Prize team has amazing effects.


In October 2017, the FDA approved the launch of the first CAR-T cell therapy. Humans have entered the era of cell therapy. CAR-T cell therapy has achieved good clinical results in blood cancers.

 

At present, several CAR-T therapies on the market use autologous T cells from the patient .

The advantage of autologous cell therapy is that it can function in the patient for a long time without causing rejection, but this method also exists.

With many limitations, autologous cell therapy is time-consuming, some acute leukemia patients do not have enough time to wait, and many severe patients do not have enough T cells themselves for engineering.

 

Therefore, many research teams and companies have begun to develop allogeneic cell therapy .

The cell source of allogeneic cell therapy is more diverse, which can be peripheral blood , umbilical cord blood , and artificial induced pluripotent stem cells (iPSC) , etc.

This method is easier to batch production, which is less time-consuming, could address many of the limitations of autologous cell therapy.

 

Among them, Caribou Biosciences , founded by Jennifer Doudna , a Nobel Prize winner and one of the founders of CRISPR gene editing technology, is one of the representatives.

 

CAR-T therapy by Nobel Prize team: The total remission rate is 100%

 

On May 12, 2022, Caribou Biosciences announced that its off-the-shelf CAR-T therapy CB-010 based on CRISPR gene editing developed in a Phase 1 clinical trial for the treatment of relapsed and refractory B-cell non-Hodgkin lymphoma . This is also the first time Caribou has published human clinical trial data.

 

Published data showed an overall response rate (ORR) of 100% and a complete response rate (CR) of 80% among the five evaluable patients .

Of the 4 patients who have achieved complete remission so far, this remains true three months after treatment, with the longest recorded complete remission at six months.

 

 

CAR-T therapy by Nobel Prize team: The total remission rate is 100%

 

It is reported that Caribou will further announce detailed data at the European Association of Hematology (EHA) annual meeting next month.

 

CB-010 therapy is an allogeneic anti-CD19 CAR-T cell therapy based on CRISPR gene editing . Gene editing using Caribou ‘s proprietary chRDNA technology, chRDNA, the CRISPR hybrid RNA-DNA technology, compared to CRISPR-Cas9, chRDNA has a high degree of specificity and a lower level of off-target editing, enabling multiple gene editing, including multiplex gene insertion.

 

CB-010 therapy performed gene editing in 3 aspects:


1. Knock CD19 CAR site-specifically into T cells;

2. Knock out the TRAC gene (T cell receptor alpha constant region) , after knockout, the T cell receptor (TCR) on the surface of T cells is cleared, which can avoid graft-versus-host reaction (GvHD) ;

3. Knock out the gene encoding PD-1 to improve the persistence of anti-tumor activity of CAR-T cells.

 

CAR-T therapy by Nobel Prize team: The total remission rate is 100% CAR-T therapy by Nobel Prize team: The total remission rate is 100%

 

 

It is reported that this is also the first allogeneic CAR-T cell therapy to knock out PD-1 in clinical studies.

 

Rachel Haurwitz , CEO of Caribou Biosciences , said that three CD19-CAR-T cell therapies (Gilead’s Yescarta, BMS’ Breyanzi, Novartis’ Kymriah) that have been approved by the FDA have been approved by the FDA .

The total response rate is 50%-70%. The remission rate is 30%-50%. The two data of CB-101 are 100% and 80% respectively.

 

In addition, CB-101 has the advantage that the dosage is much lower than the above three CAR-T cell therapies, which may be safer.

 

 

 

Rachel Haurwitz said there were no graft-versus-host reactions (GvHD) following CB-101 treatment , and most adverse events observed were grade 1 or 2, in 3 of 6 patients during the first 28 days of treatment More serious grade 3 and 4 events were observed, but they recovered within 39 hours of treatment, and overall, CB-101 was well tolerated.

 

Based on these preliminary clinical data, Caribou plans to enter a dose escalation phase, this time six patients will be infused with 40 million CAR-T cells, and the next cohort will be infused with 80 million CAR-T cells.

 

 

 

Caribou Biosciences

 

Jennifer Doudna (left) , Rachel Haurwitz (right)

 

 

Caribou Biosciences was founded in 2012 by CRISPR gene editing founder and 2020 Nobel laureate Jennifer Doudna and her student Rachel Haurwitz , who serves as the company’s CEO.

 

In July 2021, Caribou Biosciences was listed on Nasdaq, which is another listed company founded by Jennifer Doudna after Intellia Therapeutics .

 

Caribou Biosciences is committed to developing next-generation “off-the-shelf” CAR-T and CAR-NK cell therapies through CRISPR gene editing technology to solve the host immune system’s rejection of allogeneic cell therapy and benefit more cancer patients.

 

 

 

R&D pipeline

At present, Caribou has a total of 4 self-developed pipelines and 2 research and development pipelines in cooperation with AbbVie .

 

Among the self-developed pipelines, 3 are CAR-T therapy and 1 is CAR-NK therapy. The 3 CAR-T therapies are all aimed at hematological malignancies, of which CB-010 is the fastest in progress.

This CD19 – targeting CAR-T therapy is used to treat B-cell non-Hodgkin’s lymphoma and is currently undergoing 1 CAR-T therapy. Phase clinical trials.

CB-011 is currently under application for clinical trials, a CAR-T therapy targeting BCMA for the treatment of multiple myeloma.

A clinical trial application will be submitted next year for CB-012, a CAR-T therapy targeting CD137 , for the treatment of acute myeloid leukemia.

 

CB-020 is an iPSC-based CAR-NK cell therapy for the treatment of solid tumors. The specific target information will be announced in the fourth quarter of this year.

 

CB-101 uses Cas9-chRDNA editing technology, and other pipelines use Cas12a-chRDNA editing technology.

 

 

 

In addition, Caribou has two CAR-T cell therapy projects based on Cas12a-chRDNA in cooperation with AbbVie , the specific information has not been disclosed.

 

Rachel Haurwitz said that in the future, we will see more possibilities for Caribou Biosciences .

Caribou is exploring the application of precision cell therapy in diseases other than tumors, expanding iPSCs beyond NK cells, and applying the Cas12a-chRDNA platform in vivo. treat.

 

 

 

 

 

 

 

 

 

 

References:
https://www.cariboubio.com/
https://cariboubio.com/in-the-news/press-releases/abbvie-and-caribou-biosciences-announce-collaboration-and-license-agreement
https://investor.cariboubio.co

CAR-T therapy by Nobel Prize team: The total remission rate is 100%

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