Abstract
In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.
Highlights
Radiotherapy (RT) is employed in the treatment of over 50% of cancer patients [1]
The results suggest that the use of smart RT biomaterials (SRBs) loaded with CD40 mAb can boost the abscopal effect
The results of this study provide the first experimental evidence demonstrating the potential of SRBs loaded with anti-CD40 to boost abscopal responses
Summary
Radiotherapy (RT) is employed in the treatment of over 50% of cancer patients [1]. Despite continuing developments to increase therapeutic efficacy, RT is still significantly limited by normal tissue toxicity and is mainly utilized for treating localized disease sites [2,3,4]. Priming the Abscopal Effect recently, there are a growing number of studies combining RT with immunotherapy to enhance both local and metastatic tumor cell kill leveraging the immune-mediated abscopal effect [9,10,11,12,13]. This abscopal effect can enable the killing of metastatic cells, distant from the irradiated site [12]. In previous work [3], the use of smart RT biomaterials (SRBs) loaded with immunoadjuvants was proposed to boost abscopal response rates, with the potential to benefit many more patients, especially those with metastatic disease [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
