AbbVie and Caribou Biosciences, Inc. have announced that the companies have entered into a cooperation agreement and license to research and develop T-cell drugs of the chimeric antigen receptor (CAR).
The terms of the multi-year agreement will allow AbbVie to use Caribou’s generation of Cas12a clusters of regularly spaced short palindrome replicates (CRISPR) of hybrid RNA-DNA (chRDNA) genome editing technology and cell therapy to research and develop 2 new CAR T-cell therapies. AbbVie will receive exclusive rights to Cas12a for targets of its choice. Caribou will perform certain preclinical research, development and production activities for collaborative programs, while AbbVie will take care of development, commercialization and other production efforts.1.2
The $ 40 million cash advance and capital investment will be targeted at Caribou, as well as up to $ 300 million at future development, regulatory and driving milestones. In addition, there will be potential for Caribou to receive additional payments for commercial milestones and global multilevel royalties. AbbVie has the option to expand the collaboration to include an additional 2 CAR T-cell therapies for a fee.1
“Caribou’s generation of CRISPR genome editing technology widely promises the development of a new therapy,” said Dr. Rachel Haurwitz, President and CEO of Caribou in an interview with OncLive®. “The partnership with AbbVie allows Caribou to increase the number of goals and diseases that these technologies can address. It is an important opportunity to expand what we hope to do for patients. The collaboration is also an important endorsement of Caribou’s differentiated genome editing technologies of the new generation CRISPR. “
CRISPR gene editing technology uses modular biological tools to induce DNA changes in living cells. The two basic components of the CRISPR system are nuclease proteins and RNA molecules. Nuclease proteins cut DNA while RNA molecules lead nuclease to generate a double-stranded break specific to a particular site, resulting in arrangement at the target genomic site. CRISPR systems are distinguished by the presence of a class 1 multiprotein effector complex or a class 2 effector protein.2.3
CRISPR systems have been shown to achieve several different types of genetic modifications in different cell types. CRISPR techniques have achieved recombination, constructed immunity, mutagenesis, and donor-mediated gene disorder in bacterial, yeast, and filamentous fungal cells. The technique is also used to achieve RNA-guided gene regulation in multiple human cell lines with high specification and efficiency of up to approximately 50%.3.4
CRISPR systems can sometimes inadvertently edit certain genomic sites, leading to detrimental effects on cellular function. Caribou’s chRDNAs are highly specific hybrid RNA-DNA guides used in combination with CRISPR to guide more precise genome regulation.2
“Caribou uses CRISPR hybrid RNA-DNA guides that contain both DNA and RNA nucleotides,” Haurwitz explained. “These hybrid guides trigger a much more specific genome arrangement than all RNA guides. Caribou uses chRDNA guides along with the enzyme CRISPR to develop complex immune cell therapies. “
By using CRISPR technology to design CAR T-cells to withstand a host immune attack, Caribou hopes to develop “ready-made” cell therapies aimed at benefiting a wide population of patients. The company is currently focusing on genome-arranged allogeneic CAR-T cells and natural killer cell therapies to treat patients with irresistible malignancies.5
Current programs in the discovery phase include CB-011 and CB-012 which use T cells to target BCMA and CD371 for patients with hematologic malignancies. Another product, CB-020, focuses on the use of natural killer cell therapies for the undetected target of patients with solid tumors. The CB-010 program, which is currently in Study Phase 1, uses T cells to target CD19 and for patients with relapse / refractory B-cell non-Hodgkin’s lymphoma.5
“I am excited about the opportunity for our companies to jointly develop 2 additional CAR T- [cell products], expanding to the total number of therapies underlying Caribbean technologies, ”concluded Haurwitz.
- AbbVie and Caribou Biosciences announce a collaboration and license agreement for CAR-T cellular products. News. February 10, 2021 Accessed February 21, 2021 https://www.prnewswire.com/news-releases/abbvie-and-caribou-biosciences-announce-collaboration-and-license-agreement-for-car-t-cell -products-301225509.html
- Pioneering chRDNA guides. Caribou Biosciences. Retrieved February 21, 2021. https://cariboubio.com/technology
- Donohue PD, Barrangou R, May AP. Advances in industrial biotechnology using the CRISPR-cas system. Trends Biotechnologist. 2018; 36 (2): 134-136. doi: 10.1016 / j.tibtech.2017.07.007
- Cameron P, Coons MM, Stenberg SH, et al. Use of the CRISPR-Cas type I system for genome engineering in human cells. Nat Biotechnol. 2019; 37: 1471-1477. doi: 10.1038 / s41587-019-0310-0
- Pipeline. Caribou Biosciences. Retrieved February 21, 2020. https://cariboubio.com/pipeline