Solid Tumors Targeted in Next-Generation CAR T Collaboration

AdAlta and Carina Biotech are collaborating to develop next-generation, bi-specific, chimeric antigen receptor (CAR) T-cell therapies for the treatment of a range of solid tumors.

The collaboration combines Carina’s proprietary multifunctional chemokine receptor platform for creating CAR therapies with AdAlta’s i-body next-generation antibodies to create bi-specific CAR T-cell therapies for up to 5 solid tumor targets. AdAlta will discover and optimize I-body panels that bind to these targets. Carina will then develop the bi-specific CAR T-cells and identify CAR T candidates.

"We believe that by combining our i-bodies with Carina's world-class CAR-T platform, we can make this important new therapeutic approach accessible to more patients and a greater range of cancers than is possible today. We are well past the starting line, having worked previously on the first two targets selected for our collaboration, and with Carina on one of these,” Tim Oldham, PhD, chief executive officer and managing director, AdAlta, said in a statement.

AdAlta and Carina will jointly fund preclinical mouse studies. The first 2 targets of the collaboration have been selected and research is set to start in the coming months. The collaboration will continue for at least 2 years until research is completed for the final target. The companies will jointly own any products developed.

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"This collaboration with AdAlta gives us the capability to generate bi-specific CAR molecules and then next-generation CAR-T cell products with enhanced cancer targeting and efficacy – something we are very excited about. The collaboration is off to a great start with Carina having already successfully inserted an AdAlta i-body into a CAR-T cell with functional cancer killing capability," Deborah Rathjen, PhD, chief executive officer, Carina, added to the statement.

AdAlta’s i-bodies are around one-tenth the size of conventional monoclonal antibodies and thus have the potential to be effective in difficult-to-access targets. Their size also allows greater flexibility in designing the CAR T-cells. The i-bodies can also be used CAR receptor binding domain and are also around half the size of traditional binding domains, offering more flexibility in targeting. 

Carina Biotech also utilizes a concurrent activation-transduction phase when manufacturing CAR T-cells. The streamlined process greatly cuts down manufacturing time and will lend greater efficiency to the new collaboration.

"A core part of AdAlta's strategy is to enter collaborations with partners where we can further the use of our i-bodies to address disease targets previously thought undruggable. The i-body-directed CAR-T cells will be the second example of this, complementing our collaboration with GE Healthcare where i–bodies are being used to deliver a PET imaging agent. The Carina collaboration contributes multiple potential products to our pipeline expansion goals,” Oldham added to the statement.

Carina’s lead program is an LGR5-targeted CAR-T cell therapy that has shown promising data in preclinical studies for the potential treatment of advanced colorectal cancer. They expect to initiate a phase 1 clinical study in 2022. AdAlta has previously focused on developing treatments for fibrotic diseases.

REFERENCE
ASX Announcement: AdAlta and Carina Biotech to develop next-generation CAR-T cancer therapeutics. News release. August 24, 2021. https://www.biospace.com/article/releases/asx-announcement-adalta-and-carina-biotech-to-develop-next-generation-car-t-cancer-therapeutics/