Profiles in Biotech (8/30/23)

Analysis

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Synthekine develops engineered cytokine therapeutics to treat cancer and inflammatory disorders. Using protein engineering to create cytokine partial agonists, which are designed to be more safe and effective than traditional cytokines.

Founded in 2017, Synthekine's lead program is a cytokine partial agonist for cancer that is currently in Phase 1 clinical trials. The company's cytokine partial agonists are designed to have a more targeted and specific effect on the immune system than traditional cytokines. Reducing the risk of side effects.

Two distinct evolutionary conserved neural degeneration pathways characterized in a colonial chordate

The paper introduces Botryllus schlosseri, a marine colonial chordate, as a model organism for the study of neurodegeneration. Finding that B. schlosseri undergoes two distinct neurodegenerative processes during its life cycle:

- A weekly cycle of neurodegeneration that occurs independently of age. This process is associated with the death and removal of neurons in the adult brain, which is followed by the regeneration of a new brain in the newly formed buds.

- A process of neurodegeneration that is associated with colony aging. This process is characterized by a decline in the number of neurons in the brain, as well as changes in gene expression.

The authors suggest that B. schlosseri is a valuable model organism for the study of neurodegeneration because it offers several advantages, including a unique and assayable life cycle, real-time monitoring enabled by transparent body and vasculature, adult tissue-specific stem cells that can be enriched and transplanted, morphological differences associated with colony age, and a sequenced genome

Establishing B. schlosseri as a potentially powerful tool for understanding the molecular and cellular mechanisms of neurodegeneration, as well as the evolutionary origins of these processes.

https://www.pnas.org/doi/abs/10.1073/pnas.2203032119

Superagonists, partial agonists and antagonists of interleukin-2

The patent is for a new type of interleukin-2 (IL-2) molecule that is a partial agonist or antagonist of IL-2. Which is a cytokine that plays an important role in the immune system, but it can also have harmful side effects.

The new IL-2 molecule is designed to have reduced binding affinity for the IL-2 receptor that is responsible for the harmful side effects, while maintaining binding affinity for the receptor that is responsible for the beneficial effects. This makes the new IL-2 molecule a potential treatment for diseases that are caused by IL-2, such as graft-versus-host disease (GVHD) and adult T cell leukemia.

The new IL-2 molecule is created by making mutations to the amino acid sequence of wild-type IL-2. The mutations are chosen to increase the binding affinity of the molecule for the IL-2 receptor that is responsible for the beneficial effects, and to decrease the binding affinity of the molecule for the IL-2 receptor that is responsible for the harmful side effects.

https://patentimages.storage.googleapis.com/12/27/5e/f2863f2a04e913/US20230002467A1.pdf

How are chimeric antigen receptors created?

Chimeric antigen receptors (CARs) are created by fusing three different components:

1. An antigen-binding domain, which is derived from a monoclonal antibody or other molecule that can specifically recognize a tumor cell antigen.

2. A transmembrane domain, which allows the CAR to be anchored to the surface of the T cell.

3. An intracellular signaling domain, which activates the T cell when the CAR binds to its target antigen

Using molecular cloning, the three components of the CAR are first isolated and then combined into a single molecule. This molecule can then be introduced into T cells using a variety of methods, such as viral transduction or electroporation.

Once the CAR has been introduced into the T cells, they are cultured and expanded. This allows the number of CAR-expressing T cells to increase by several orders of magnitude. The CAR-expressing T cells are then infused back into the patient, where they can target and destroy tumor cells.

Scientists are working to improve the specificity, potency, and durability of CAR-T cells. With the first-generation of CARs having a single-chain variable fragment (scFv) as the antigen-binding domain. ScFvs are small antibody fragments that can bind to a specific antigen with high affinity. Second-generation CARs: these CARs have additional signaling domains, such as CD28 or 4-1BB, that can enhance the activation and proliferation of CAR-T cells. Third-generation CARs: have been designed to target tumor cells that have become resistant to first- and second-generation CAR-T cells.

Scientist Stories: Christopher Garcia, Co-Founder of Synthekine

Garcia is a professor at Stanford

Synthetically leveraging natural biological signaling mechanisms as a path to potential therapeutics