Our research paper ‘Combined local immunostimulatory radioisotope therapy and systemic immune checkpoint blockade imparts potent antitumour responses’ was published in Nature Biomedical Engineering (Nat. Biomed. Eng. 2018, DOI: 10.1038/s41551-018-0262-6).
In this work, Catalase (Cat), an enzyme that converts tumor endogenous H2O2 into oxygen, is labeled with a therapeutic radioisotope 131Iodine, and then mixed with sodium alginate (ALG) as well as an immune-adjuvant CpG oligonucleotide (Figure 1). In this system, ALG, as a soluble polysaccharide, could be rapidly transformed into a gel in the presence of Ca2+ ions after local administration into tumors, leading to long-term fixing of the other components inside the tumor. Cat is able to decompose tumor endogenous H2O2 to increase the oxygen level within the tumor. CpG works as an adjuvant to promote the immune responses of tumor-associated antigens after tumors are destructed by 131I-radiotherapy. As a result, 100% tumor elimination efficacy under rather low radioactivity doses could be achieved in a mouse tumor models, a patient-derived xenograft model, and a rabbit tumor model. Furthermore, local treatment with a 131I-Cat/CpG/ALG hybrid fluid after eliminating local tumors could trigger systemic antitumor immune responses, which in combination with checkpoint-blockade would attack distant tumors for metastasis inhibition. Afterwards, a strong vaccine-like immunological memory effect to protect mice against tumor re-challenging is further realized.
Our new radioisotope-immunotherapy strategy can manage large solid tumors, eliminate spreading metastatic tumors, and induce immune-memory effect to prevent tumor recurrence in mouse and rabbit tumor models. This method may have potential to treat many types of solid tumors, and would be particularly meaningful for those late-stage cancer patients that are not cured by conventional surgery or radiotherapy strategies. One important note is that all the components used in this strategy are biocompatible; our next major goal is to push this biomaterials-based radioisotope-immunotherapy strategy into clinical translation.
Mailing Address: Soochow University Dushu-Lake Campus,Box 33,199 Ren'ai Rd,Suzhou Industrial Park,Suzhou,jiangsu,215123,P.R.China
Courier: Institute of Functional Nano and Soft Materials,Soochow University Dushu-lake Campus,199 Ren'ai Rd,Suzhou industrial Park,Suzhou,jiangsu,215123,P.R.China
Postcode: 215123
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