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Caribou results suggest renewed promise for ‘off-the-shelf’ cancer cell therapy

Dive Brief: An “off-the-shelf” cancer cell therapy developed by Caribou Biosciences induced responses in more than 80% of enrollees in an early-stage trial in lymphoma, similar to the response rates seen with personalized treatments manufactured from patients’

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Dive Brief:

  • An “off-the-shelf” cancer cell therapy developed by Caribou Biosciences induced responses in more than 80% of enrollees in an early-stage trial in lymphoma, similar to the response rates seen with personalized treatments manufactured from patients’ own immune cells, the company said Monday.
  • The trial data will support plans by Caribou to run a Phase 3 trial that will evaluate its treatment’s impact on survival and report results in 2026. The results offer the chance at a turnaround for Caribou, which initially reported disappointing findings but has since refined its strategy by using donor cells more compatible with patients’ immune systems.
  • Caribou has twice cut staff over the last two years to extend its cash reserves, and decided against pursuing autoimmune cell therapy as many of its peers have done. Company shares rose by as much as 40% in Monday morning trading before settling into a smaller double-digit gains.

Dive Insight:

If successful, donor-derived or “allogeneic” cell therapies could prove attractive to patients and physicians by reducing the complexity and waiting times involved in making treatments out of a person’s immune cells. But many companies have tried to prove the technology could yield a more convenient alternative to these “autologous” treatments, only to see their products underwhelm in clinical testing. Caribou believes it may have found an answer, though. By “matching” proteins called human leukocyte antigens, or HLAs, on donor cells to the patients in its trials, Caribou hopes that its treatments won’t be shut down by the immune system. The data disclosed Monday are the first evidence in support of that theory. The data came from two groups of enrollees in a trial called Antler, which tested the treatment, called vispacabtagene regedleucel or vispa-cel, in people whose diffuse large B-cell lymphoma resisted first-line treatment or returned afterward. As of a Sept. 2 data cutoff, 82% of people with four or more “matched” HLAs responded, 64% went into total remission, and 51% of them lived 12 months without their disease progressing. A second cohort that got “optimized” CAR-T cells had similar results. In that study cohort, 86% responded, 63% had a complete remission, and 53% lived 12 months without disease progression. In both groups, more than half were still responding to treatment as of the data cutoff date. While cross-trial comparisons can be misleading, Gilead’s marketed lymphoma therapy Yescarta had an 83% response rate and a complete remission rate of 65% in a similar group of patients . Caribou said vispa-cel recipients had low rates of immunological and neurological side effects in the study, indicating the treatment could be administered in outpatient settings. People receiving autologous cell therapy often have to stay in a hospital for close monitoring because of such side effects. “This clinical dataset demonstrates vispa-cel’s efficacy and durability are comparable to autologous CAR-T therapies, yet its off-the-shelf availability and favorable tolerability profile make it well suited for outpatient administration at both large academic centers and sophisticated community hospitals,” said Mehdi Hamadani, a trial investigator and professor at the Medical College of Wisconsin, in a statement. The results “validate” Caribou’s HLA-matching approach, wrote Leerink Partners analyst Mani Foroohar in a Monday note to clients. The findings also represent “the upside case for vispa-cel,” which would be a profile “on par” with personalized treatments while offering logistical advantages and lower production costs, he added.

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01Why Muscle Cells Might Do Some Heavy Lifting

Brown was studying gene therapy in the 1990s when he designed a technology to turn mRNA expression on or off in different cells. For the new mouse study, published in Nature Biotechnology , he adapted the technology to turn off mRNA expression in dendritic cells, muscle cells, or liver cells. The researchers then vaccinated the mice with each version, delivering the vaccines both intravenously and intramuscularly. “The results were pretty stunning,” Brown said. When mRNA expression was turned off in muscle cells, T-cell response went down, suggesting muscle cells play a role in immunity. When expression was turned off in liver cells, T-cell expression tripled — indicating liver cells dampen immunity. Turning off expression in dendritic cells had no effect on T-cell activation, though it did reduce the number of killer T cells by as much as half. (Interestingly, no such reduction occurred when the antigen was SARS-CoV-2 spike. Brown is now investigating why different antigens had varying effects.) Knowing all this is crucial for designing effective mRNA vaccines and therapies. That’s because different mRNA therapies require different strategies. Cancer vaccines must boost tumor-fighting killer (CD8+) T cells. For genetic disease treatments, scientists want to avoid triggering the immune system to prevent killing the very cells the mRNA is meant to modify. “Understanding the immunology is extremely important for this class of drug,” Brown said. The finding doesn’t mean dendritic cells aren’t important for mRNA vaccines to work. “It just means that the mRNA doesn’t have to get into those cells to induce an immune response,” Brown said. Instead, the antigen can be transferred to those dendritic cells.

Source: www.medscape.com ↗
02Lifestyle Matters: How do environmental and lifestyle factors influence Alzheimer’s disease?

Dr. Harrison and Finnish neuroscientist Dr. Miia Kivipelto explore the complex interplay between genetics and lifestyle in Alzheimer's development. Learn how the groundbreaking FINGER study demonstrates potential prevention strategies, and discover the latest evidence on how environmental factors, diet, and chronic conditions influence Alzheimer's risk.

Source: www.biopharmadive.com ↗
03What Comes Next

With data expected in the fourth quarter of 2026, we are prioritizing histology alongside patient-reported outcomes using the Celiac Disease Symptom Diary, one of only two instruments developed in line with U.S. Food and Drug Administration (FDA) guidance, to capture changes in symptoms such as abdominal pain and nausea. Ultimately, the broader aim is to give gastroenterologists and patients a therapeutic option for a disease that has long been managed without one. The future of drug development will not be defined by statistical significance alone, but by whether new therapies also improve the daily burden of living with celiac disease. “The first therapy to cross the line could change the field,” Geller concluded. “It would help establish celiac as a serious medical condition with options beyond a restrictive diet and open the door for what comes next.” Dr. Paul Lizzul is chief medical officer at First Tracks Biotherapeutics, a clinical ‑ stage biotechnology company advancing antibody therapeutics that modulate immune pathways implicated in autoimmune and inflammatory diseases. Marilyn Geller serves as an advisor to First Tracks Bio. Footnotes Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev . 2014;260(1):221-234. https://doi.org/10.1111/imr.12191. Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci U S A . 2009;106(37):15849-15854. https://doi/full/10.1073/pnas.0908834106. Anthony S, Schluns KS. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation. Research and Reports in Biology . 2015;6:25-37. https://doi.org/10.2147/RRB.S57685.

Source: www.biopharmadive.com ↗
04What the Artificial Neuron Cannot Do

Hersam’s next goal is a small circuit — perhaps 10 artificial neurons — where each one fires differently, and together they accomplish what would require thousands of conventional transistors. “ Silicon achieves complexity by having billions of identical devices,” Hersam said. “The brain is the opposite. It’s heterogeneous. The complexity is at the device level.” But Gaudet sees a gap no circuit design can yet fill: Biological neurons grow new connections and prune old ones, strengthening pathways that are used and weakening those that aren’t. Hersam’s lab’s printed neurons — or any other neuromorphic technology that mimics neuronal dynamics — can’t achieve that level of complexity yet. Brown is careful about the distance remaining between these printed neurons and the real thing. “Neurons are just so flexible,” he said. “They can totally change what they’re doing based on whether they’ve learned something and based on your emotional state. There’s a lot of hidden mysteries.” Sangwan suspects the device has more to reveal. “It’s a nonlinear dynamical system,” he said. “We don’t fully know how many different variables you need to explain it. It’s just the beginning.” Hersam, Sangwan, Brown, Holla, and Gaudet reported having no relevant financial disclosures. Disclosure information for study authors is available in the original study publication.

Source: www.medscape.com ↗
05China: Threat or opportunity?

One of the biggest biotech news stories of recent years is China’s continued rise as a biotech and life sciences powerhouse. China conducts a quarter of all clinical trials and drug development and has almost 1,500 new drugs in development.¹ Many China-based biotechs have benefitted from government funds, out-licencing deals with large pharmas and venture capital funding. However, policymakers in the US and EU have concerns about the possible threat to their region’s biosecurity and competitiveness as centres for health and life science research. Given China’s increased importance, ICON Biotech conducted the same biotech sector survey with 100 China-based biotech leaders. The results show that Chinese biotechs face many of the same challenges as biotechs located elsewhere. They share the same funding challenges and burdens associated with increasingly complex clinical trials and regulations.

Source: www.biopharmadive.com ↗
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Peptide Therapy Guide Editorial Team

Editorial team for Peptide Therapy Guide.

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