Bristol Myers Ends Cellares Manufacturing Agreement
Bristol Myers Squibb has ended its partnership with Cellares for the commercial-scale manufacture of the CAR T-cell therapy Breyanzi.
The companies signed an agreement worth up to $380 million in 2024, reserving manufacturing capacity in the US, European Union, and Japan. Bristol Myers said that, following an evaluation, Cellares’ automated Cell Shuttle platform could not meet the requirements of Breyanzi’s approved commercial manufacturing process.
Cellares disputed that assessment, stating that Cell Shuttle has already manufactured GMP-compliant drug product for an FDA-regulated clinical program, with doses meeting release specifications and administered to patients.
The loss of the partnership will result in approximately 100 job cuts at Cellares’ South San Francisco facility. Bristol Myers said its decision applies specifically to Breyanzi and its established manufacturing process. Source
Sickle Cell Gene Therapy Cuts Collection and Manufacturing Times
A first-in-human gene therapy study has demonstrated a faster process for collecting, modifying, and returning blood stem cells to patients with sickle cell disease.
The lentiviral therapy modifies a patient’s own stem cells to reactivate fetal hemoglobin production while suppressing the mutated adult hemoglobin gene responsible for sickle cell disease.
Ten of the 11 participants provided enough stem cells in a single collection session whereas . Commercial gene therapies can require up to five sessions. The modified cells were returned to patients after an average of seven weeks, compared with manufacturing timelines that can extend to six months or longer.
Follow-up now extends to seven years, with no unexpected safety events or adverse effects attributed to the genetic modification. A further Phase II study has completed enrollment with 25 participants, while the FDA has authorized an Expanded Access Program allowing additional patients to receive the therapy before a potential biologics license application.
The technology has also been licensed to the nonprofit Caring Cross, which is opening trials in Brazil and India. Source
Removing Immune “Brake” Strengthens CAR T Cells Against Osteosarcoma
Deleting the Regnase-1 gene from CAR T cells improved tumor control and prevented lung metastasis in preclinical models of osteosarcoma.
Researchers at St. Jude Children’s Research Hospital removed Regnase-1, which normally restrains immune activity, from B7-h4-directed CAR T cells. Nearly all mice receiving the edited cells survived, while untreated animals and those given conventional CAR T cells succumbed to disease.
When osteosarcoma cells were reintroduced months later, the surviving mice continued to reject the tumors, suggesting that the treatment produced a durable immune response.
The modified cells also remodeled the tumor microenvironment. They increased the presence and activity of other immune cells while reducing immunosuppressive cells and signaling. St. Jude is now developing an early-phase clinical trial of the approach. Source
CD40 Stimulation Improves CAR T Activity in Solid Tumors
Combining CAR T-cell therapy with a CD40 agonist improved tumor control and survival in mouse models of pancreatic and triple-negative breast cancer.
Researchers tested mesothelin-directed CAR T cells alongside an agonistic CD40 antibody designed to activate antigen-presenting cells and mobilize the wider immune system.
The combination produced more sustained tumor necrosis, increased immune-cell activation within tumors and systemically, and improved survival compared with CAR T cells alone. It also reduced regulatory T-cell frequencies and increased the presence of effector immune cells within the tumor.
The approach was evaluated in immunocompetent models of pancreatic ductal adenocarcinoma and triple-negative breast cancer. Although it did not completely control every pancreatic tumor, it produced durable immunity and superior tumor control in the breast cancer model. Source
Bioinspired Nanoparticles Deliver Cholesterol Gene Editing
A lipid nanoparticle made from biologically inspired materials has delivered a base editor to the liver and reduced LDL cholesterol in preclinical models.
Researchers combined naturally occurring polyamines with oleic acid to create a carrier for mRNA encoding an adenine base editor targeting PCSK9, a gene that regulates LDL cholesterol.
The strongest-performing formulation carried approximately 98 percent of its mRNA payload and edited around 68 percent of the intended PCSK9 target in cultured cells. Two intravenous doses reduced LDL and total cholesterol by more than 20 percent in high-fat-diet models.
The nanoparticles produced fewer markers associated with inflammation and cell damage than comparator formulations, with no detectable additional liver damage. The researchers said longer-term studies and broader assessments of possible off-target editing will be required before human trials. Source
4basebio and Genezen Expand Viral Vector Collaboration
4basebio and Genezen have expanded their collaboration to provide viral vector developers with access to synthetic, cell-free DNA starting materials.
Under the non-exclusive agreement, Genezen will offer 4basebio’s research-use, high-quality, and GMP-grade hpDNA for programs ranging from early development to clinical and commercial manufacturing.
4basebio’s enzymatic manufacturing process removes bacterial backbone sequences and antibiotic resistance genes found in conventional plasmid DNA. In AAV production, the company says its hpDNA has delivered comparable titers while requiring approximately 30 percent less DNA and transfection reagent.
The partners also expect the cell-free process to shorten DNA production timelines and help developers establish manufacturing strategies suitable for later-stage development. Source
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