Kite, the Gilead subsidiary specializing in CAR-T, is trying out epigenetic editing as it seeks new ways to create next-generation cell therapies that are more effective against cancer.

Teaming up with California-based Epic Bio, Kite will tap its new partner’s technology to engineer T cells by tinkering with gene expression — in hopes of “in essence, overcoming more than one tumor challenge with one technology,” said David Barrett, Kite’s vice president of cell biology and translational medicine.

The companies are keeping the financial terms of the deal under wraps, but Epic Bio CEO Amber Salzman said the undisclosed upfront will help extend the biotech’s cash runway. It also marks the first epigenetic editing partnership with a direct application, she said.

Epic Bio is tasked with screening for CRISPR constructs — complete with a guide RNA that would locate the gene of interest, a Cas molecule that would bind to the DNA, and a tiny peptide that would modulate the expression of that gene. Kite has identified several targets it’s interested in upregulating or downregulating; Salzman notes the same approach can be applied to solve numerous bottlenecks in cell and gene therapy.

“The limitation is really just understanding your disease and knowing which targets to go after,” she said.

Epic Bio and fellow epigenetic editing players such as Chroma Medicine and Tune Therapeutics are putting a twist on the concept of gene editing with the promise of delivering lasting changes to the genome without making changes to the DNA. The deal with Kite is being unveiled on the same day the FDA is convening a panel of experts to discuss a sickle cell therapy from Vertex and CRISPR Therapeutics, which could be the first CRISPR gene editing treatment to come to the market.


‘Hyper-compact’ Cas

Compared to its peers, Epic Bio said its CRISPR/Cas constructs — licensed out of Stanford from co-founder Stanley Qi — are unique for their compact size. Qi, who worked with CRISPR maven Jennifer Doudna, developed CasMINI, which, at 529 amino acids, is about half the size of the commonly used Cas9. Epic Bio has further engineered them to be under 500 amino acids, according to Dan Hart, head of technology development.

Whereas traditional CRISPR/Cas9 constructs are too large for certain delivery methods, the hyper-compact CasMINI derivatives — sometimes more than one of them — can “fit comfortably in a single AAV,” Salzman said. They can also be delivered in other vectors, such as a lentivirus, retrovirus or even lipid nanoparticles. The fact that one can fit multiple of them in the same vector allows cell therapy makers to make several desired changes in one go instead of having to transfect T cells multiple times, as she recalled hearing at conferences.

“This means you can target multi pathways that may be the target of tumor suppressive signals, that impede good T cell function or otherwise reduce the efficacy of your CAR therapy,” Kite’s Barrett told Endpoints in an email. “You do not have to insert whole transgenes like in other strategies, and the multiplexing ability gives a lot of freedom to adapt this approach to not just lymphoma but to solid tumors as well.”

The multiplex capability will be key, he added, as the field looks to the future of synthetic biology to overcome cancer cells’ resistance mechanisms to immunotherapy, with the goal of putting multiple elements — from CAR to armors like dominant negative cytokine receptors and logic gate systems on the same T cells.

Epic Bio expects to come up with the constructs to be used in Kite’s CAR-T cells within six to 12 months. Meanwhile, it will also be pushing forward its internal pipeline, which is focused on modulating genes in vivo, with the goal of dosing its first patient next year.

About PackGene

PackGene is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha 293 cell AAV high-yield platform and the π-Omega plasmid high-yield platform. PackGene's mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.

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