Durable Therapeutics for Chronic Inflammatory Diseases
Generating antibody-based therapeutics for severe allergy and asthma, chronic obstructive pulmonary disease, eosinophilic esophagitis, food allergies and atopic dermatitis
Technology Overview
Dr. James M. Olson
Many chronic inflammatory conditions are initiated or exacerbated by a cascade of reactions launched by cytokines binding to the thymic stromal lymphopoietin protein receptor (TSLPR). Food allergens trigger an inappropriate TSLPR response in eosinophilic esophagitis, a chronic inflammation of the esophagus, in the same way that airborne agents can trigger severe asthma. Clinical guidance for these and other chronic inflammatory diseases includes avoiding specific foods, environments or activities — which can be challenging for patients, especially pediatric patients. Another treatment option is steroid therapy, which can have harmful side effects such as changes in blood pressure or blood sugar, and susceptibility to infections. Current treatments that block TSLPR require weekly injections.
Supported by funding from the Washington Research Foundation, pediatric neuro-oncologist James M. Olson, MD, PhD, and Invent Entrepreneur Sinduja Marx, PhD, are developing long-acting therapies for adults and children with chronic conditions such as severe asthma and allergies, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and atopic dermatitis. The innovative therapies are based on dozens of unique, fully humanized anti-TSLPR monoclonal antibodies.
Elements of the monoclonal antibodies could be used in cellular immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy. Other potential applications include as antibody-drug conjugates (ADCs) or antibody-dependent cellular cytotoxicity and cellular phagocytosis agents. Drs. Olson and Marx also are exploring one-time gene therapies that give the patient’s own cells the ability to block immune overreaction. Furthermore, TSLPR is overexpressed in several types of cancers, including some leukemias and breast and colon cancers, suggesting broader applications for these therapeutics.
To increase the usefulness of the monoclonals, the research team expanded the original collection to create new binding proteins with varying TSLPR affinity. Many of antibodies have cross-species reactivity and the Olson and Marx team have expertise in characterizing therapeutic candidates structurally and functionally (e.g., in vitro with inflammatory cells, and in vivo in animal models).
For therapeutics such as ADCs and CAR T cells, the Olson Lab has expertise in creating bispecific and multispecific antibody-based binding molecules. These binders can recognize multiple targets such as two or more cell-surface markers, leading to more precise therapeutic delivery and increased effectiveness. The Olson Lab is optimizing binding domains for greater specificity and stability and can generate antibodies in formats that facilitate scale-up and manufacturing.
Dr. Olson has cofounded several biotech companies. Drs. Olson and Marx are interested in partnerships that take advantage of the Olson Lab’s extensive experience working with industry partners. They are open to partnerships or collaborations to advance development, preclinical and clinical testing, and clinical delivery of TSLPR antibody-based therapies.
Stage of Development
- Preclinical in vitro
- Preclinical in vivo
Partnering Opportunities
- Collaborative research and development
- Sponsored research agreement
- Consultation agreement
- Licensing agreements
Publications
Simon S, Bugos G, Prins R … Olson JM, et al. Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy. Nat Cancer. 2025;6(4):647-665.
Jamet S, Zhang H, Ditzler S … Olson JM, et al. Affinity-tuned T-cell engager for dual targeting of B-myeloid mixed-phenotype acute leukemia (B-MPAL). Blood. 2024;144 (Suppl. 1):90.
Marx SK, Mickolajczyk KJ, Craig JM, et al. Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution. Nucleic Acids Res. 2023;51(17):9266-9278.
Vorobieva AA, White P, Liang B … Marx S, et al. De novo design of transmembrane β barrels. Science. 2021;371(6531):eabc8182.
Cook Sangar ML, Girard EJ, Hopping G … Olson JM. A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure. Sci Transl Med. 2020;12(533):eaay1041.
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