Caribou to test off-the-shelf CAR-T in lupus

2024-04-05

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Caribou Biosciences is the latest cell therapy developer to jump on the autoimmunity hype train. The company said the FDA has cleared a safety trial of its allogeneic CD19-targeting CAR-T cell therapy in certain patients with lupus, with the study expected to kick off by year-end.

The Phase I GALLOP trial will enrol patients with lupus nephritis (LN) and extrarenal lupus (EL) to receive CB-010. The cell therapy is engineered with Caribou’s Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to have a PD-1 knockout, which is intended to reduce CAR-T cell exhaustion.

The study will employ partial human leukocyte antigen (HLA) matching between patients and iterations of the donor-derived off-the-shelf cell therapy, which Caribou said may improve clinical outcomes based on data from the ANTLER study, an ongoing Phase I trial of CB-010 to treat relapsed/refractory B cell non-hodgkin lymphoma.

HLAs act “as our body’s identity card to know one’s ‘self’ from ‘not self,’” said Mehdi Hamadani, an investigator for ANTLER. “In stem cell transplants, it has been shown that a close HLA match between patients and donors significantly reduces the rejection of the therapy. This same logic can be applied to allogeneic CAR-T cells as well, so that the activity of the therapy persists long enough to target and destroy the diseased cells.”

Caribou’s move to test CB-010 in lupus follows a larger trend from biotechs and large pharmas alike to explore the potential of certain cancer cell therapies to treat autoimmune diseases. Partially fueling the movement is early clinical data from a team of German scientists that found a CD19 CAR-T led to over two years of remission for patients with systemic lupus erythematosus (SLE).

Vasileios Kyttaris, rheumatology specialist and assistant professor of medicine at Beth Israel Deaconess Medical Center, told FirstWord that lupus patients would need to experience, at a minimum, two to four years of drug-free remission for the intensive therapy to catch on.

The relatively new space is also attracting investor interest. Kyverna Therapeutics successfully spun its autoimmune cell therapy pipeline into what is so far the year’s second biggest IPO. “Two years ago, it wasn’t clear that targeting CD19 for autoimmune disease would create such a big buzz. People are now starting to take notice,” chief executive Peter Maag told FirstWord in an interview last month. For more, see ViewPoints: Kyverna CEO outlines next steps for autoimmune CAR-T pipeline.

Other cell therapy modalities are also following suit. Last month, Nkarta said it would halt most development activities for its allogeneic CAR-NK cell therapy NKX019 in cancer and instead focus on autoimmune diseases, and LN in particular.

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