Programmable bacteria induce durable tumor regression and systemic antitumor immunity
| Autor: | Taylor E. Hinchliffe, Nicholas Arpaia, Sreyan Chowdhury, Courtney Coker, Tal Danino, Samuel Castro |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment CD47 Antigen Article General Biochemistry Genetics and Molecular Biology Metastasis Mice 03 medical and health sciences Synthetic biology 0302 clinical medicine Immune system In vivo Neoplasms Escherichia coli medicine Animals Humans 030304 developmental biology Mice Inbred BALB C 0303 health sciences Tumor microenvironment Bacteria biology CD47 Abscopal effect Equipment Design General Medicine Immunotherapy Single-Domain Antibodies biology.organism_classification medicine.disease 3. Good health 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Genetic Engineering Hydrocephalus |
| Zdroj: | Nature medicine |
| DOI: | 10.1101/561159 |
| Popis: | SUMMARY PARAGRAPHSynthetic biology is driving a new era of medicine through the genetic programming of living cells1,2. This transformative approach allows for the creation of engineered systems that intelligently sense and respond to diverse environments, ultimately adding specificity and efficacy that extends beyond the capabilities of molecular-based therapeutics3–5. One particular focus area has been the engineering of bacteria as therapeutic delivery systems to selectively release therapeutic payloads in vivo6–8. Here, we engineered a non-pathogenic E. coli to specifically lyse within the tumor microenvironment and release an encoded nanobody antagonist of CD47 (CD47nb)9, an anti-phagocytic receptor commonly overexpressed in several human cancers10,11. We show that intratumoral delivery of CD47nb by tumor-colonizing bacteria increases activation of tumor-infiltrating T cells, stimulates rapid tumor regression, prevents metastasis, and leads to long-term survival in a syngeneic tumor model. Moreover, we report that local injection of CD47nb bacteria stimulates systemic antitumor immune responses that reduce the growth of untreated tumors – providing, to the best of our knowledge, the first demonstration of an abscopal effect induced by a bacteria cancer therapy. Thus, engineered bacteria may be used for safe and local delivery of immunotherapeutic payloads leading to systemic antitumor immunity. |
| Databáze: | OpenAIRE |
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