Caribou and AbbVie Initiate Development Partnership for CAR T-Cell Products

Article

February 23, 2021 - AbbVie and Caribou Biosciences, Inc have entered into a collaboration and license agreement for the research and development of chimeric antigen receptory T-cell therapeutics.

AbbVie and Caribou Biosciences, Inc have announced that the companies have entered into a collaboration and license agreement for the research and development of chimeric antigen receptor (CAR) T-cell therapeutics.

The terms of the multi-year agreement will allow AbbVie to utilize Caribou’s next-generation Cas12a clusters of regularly interspaced short palindromic repeats (CRISPR) hybrid RNA-DNA (chRDNA) genome editing and cell therapy technologies to research and develop 2 new CAR T-cell therapies. AbbVie will be given exclusive rights to Cas12a for the targets of their choosing. Caribou will perform certain pre-clinical research, development, and manufacturing activities for the collaboration programs, while AbbVie will handle development, commercialization, and other manufacturing efforts.1,2

A $40 million upfront cash payment and equity investment will be directed to Caribou, as well as up to $300 million in future development, regulatory, and launch milestones. Additionally, there will be the potential for Caribou to receive additional payments for commercial milestones and global tiered royalties. AbbVie has the option to expand the collaboration to include an additional 2 CAR T -cell therapies for a fee.1

“Caribou’s next-generation CRISPR genome editing technologies hold broad promise for new therapy development,” Rachel Haurwitz, PhD, president and CEO of Caribou said in an interview with OncLive®. “A partnership with AbbVie allows Caribou to increase the number of targets and diseases addressable by these technologies. It’s an important opportunity to expand upon what we hope to do for patients. The collaboration is also an important validation of Caribou’s differentiated next-generation CRISPR genome editing technologies.”

CRISPR gene editing technology utilizes modular, biological tools to induce DNA changes in living cells. The 2 basic components of CRISPR systems are the nuclease proteins and the RNA molecules. The nuclease proteins cut DNA while the RNA molecules guide the nuclease to generate a site-specific, double-stranded break, which result in editing at the targeted genomic site. CRISPR systems are differentiated by the presence of a class 1 multiprotein effector complex or a class 2 single effector protein.2,3

CRISPR systems have been shown to achieve several different types of genetic modifications in different types of cells. CRISPR techniques have achieved recombination, engineered immunity, mutagenesis, and donor-mediated gene disruption in bacteria, yeast, and filamentous fungi cells. The technique has also been used to achieve RNA-guided gene editing in multiple human cell lines with high specify and efficiencies of up to approximately 50%.3,4

CRISPR systems can sometimes unintentionally edit certain genomic sites, leading to harmful effects on cellular function. Caribou’s chRDNAs are highly specific RNA-DNA hybrid guides that are used in combination with CRISPR to direct more precise genome editing.2

“Caribou utilizes CRISPR hybrid RNA-DNA guides that contain both DNA and RNA nucleotides,” Haurwitz explained. “These hybrid guides drive much more specific genome editing than all RNA guides. Caribou uses chRDNA guides in concert with a CRISPR enzyme to develop complex immune cell therapies.”

By using CRISPR technology to engineer CAR T-cells to withstand host immune attack, Caribou hopes to develop “off-the-shelf” cellular therapies aimed at benefitting a broad patient population. The company is currently focusing on genome-edited off-the-shelf allogenic CAR T-cell and natural killer cell therapies for the treatment of patients with intractable 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, respectively. Another product, CB-020, focuses on using natural killer cells therapies for an undisclosed target for patients with solid tumors. The CB-010 program, currently in phase 1 exploration, uses T cells to target CD19 and for patients with relapsed/refractory B-cell non-Hodgkin lymphoma.5

“I am excited about the opportunity for our companies to collaboratively develop 2 additional CAR T- [cell products], expanding upon the total number of therapies Caribou’s technologies underpin,” Haurwitz concluded.

References

  1. AbbVie and Caribou Biosciences announce collaboration and license agreement for CAR-T cell products. News release. 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
  2. Pioneering chRDNA guides. Caribou Biosciences. Accessed February 21, 2021. https://cariboubio.com/technology
  3. Donohue PD, Barrangou R, May AP. Advances in industrial biotechnology using CRISPR-cas systems. Trends Biotechnol. 2018;36(2):134-136. doi:10.1016/j.tibtech.2017.07.007
  4. Cameron P, Coons MM, Stenberg SH, et al. Harnessing type I CRISPR-Cas systems for genome engineering in human cells. Nat Biotechnol. 2019;37:1471-1477. doi:10.1038/s41587-019-0310-0
  5. Pipeline. Caribou Biosciences. Accessed February 21, 2020. https://cariboubio.com/pipeline
Related Videos
Francesco Di Meo, PhD
Jay Spiegel, MD
In this fifth episode of OncChats: Leveraging Immunotherapy in GI Malignancies, Toufic Kachaamy, MD, of City of Hope, Sunil Sharma, MD, of City of Hope, and Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, discuss next steps for research, including vaccination strategies, personalized cellular therapies, and more.
In this fourth episode of OncChats: Leveraging Immunotherapy in GI Malignancies, experts discuss research efforts being made with organoids to address existing questions with immunotherapy and the exploration of multimodality approaches to improve outcomes.
In this third episode of OncChats: Leveraging Immunotherapy in GI Malignancies, Toufic Kachaamy, MD, of City of Hope, Sunil Sharma, MD, of City of Hope, and Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, discuss the potential benefits of utilizing immunotherapy approaches earlier on in the disease course.
In this second episode of OncChats: Leveraging Immunotherapy in GI Malignancies, Toufic Kachaamy, MD, of City of Hope, Sunil Sharma, MD, of City of Hope, and Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, explain the challenges faced with preventing or detecting these cancers early and the understanding that is needed to develop effective early detection methods and move the needle forward.
In this first episode of OncChats: Leveraging Immunotherapy in GI Malignancies, Toufic Kachaamy, MD, of City of Hope, Sunil Sharma, MD, of City of Hope, and Madappa Kundranda, MD, PhD, of Banner MD Anderson Cancer Center, discuss the potential for early detection multiomic assays and the work that still needs to be done to encourage their widespread use.
Tatyana Feldman, MD
Related Content
FDA

FDA Requires Boxed Warning for Risk of T-Cell Malignancies With Approved CAR T-Cell Therapies

April 19th 2024
Article
Brentjens on the Next Chapter of CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

Brentjens on the Next Chapter of CAR T-Cell Therapy in Relapsed/Refractory Multiple Myeloma

October 10th 2022
Podcast
Eric S. Christenson, MD, assistant professor, oncology, Johns Hopkins Medicine

Early Data With Copanlisib/Nivolumab Combo Support Further Exploration in MSS CRC

April 18th 2024
Article
FDA Approval Insights: Liso-Cel in Second-Line Relapsed/Refractory LBCL

FDA Approval Insights: Liso-Cel in Second-Line Relapsed/Refractory LBCL

July 28th 2022
Podcast
Ritu Salani, MD

Clinicians Turn Their Focus to pMMR Disease Following Immunotherapy’s Entrance Into dMMR Endometrial Cancer

April 16th 2024
Article
Matthew Galsky, MD

Adjuvant Nivolumab Provides Sustained DFS Benefit, Favors OS in Muscle-Invasive Urothelial Cancer

April 16th 2024
Article