Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants

Area of Science:

• Biomaterials Science
• Immunotherapy
• Radiation Oncology

Background:

• Radiotherapy (RT) is a cornerstone of cancer treatment, but its efficacy can be limited by the abscopal effect, where localized treatment leads to systemic anti-tumor responses.
• Current RT biomaterials are inert and primarily used for geometric accuracy during treatment delivery.
• Boosting the abscopal effect could enhance local RT efficacy and potentially treat metastatic disease.

Purpose of the Study:

• To investigate the efficacy of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for enhancing the abscopal effect of local radiotherapy.
• To evaluate the potential of SRBs to improve tumor growth inhibition and survival in a preclinical model.

Main Methods:

• SRBs were developed using a biodegradable polymer loaded with anti-CD40 monoclonal antibody (mAb) as an immunoadjuvant.
• Murine lung (LLC1) tumors were established on both flanks of mice, with one flank representing metastasis.
• Mice were randomized into eight cohorts receiving image-guided RT (IGRT) at 5 Gy or 0 Gy, with or without SRBs loaded with anti-CD40 mAb.

Main Results:

• SRBs loaded with anti-CD40 mAb and IGRT significantly enhanced tumor growth inhibition in the non-irradiated flank tumors, indicating a boosted abscopal effect.
• Treatment with SRBs loaded with anti-CD40 mAb, even without RT, induced an immune response.
• Complete tumor regression was observed in 60% of mice treated with SRBs, compared to 10% with anti-CD40 mAb alone and none in other cohorts.

Conclusions:

• Multifunctional SRBs loaded with immunoadjuvants can effectively boost the abscopal effect of radiotherapy, leading to enhanced tumor regression.
• These SRBs hold potential as replacements for current inert RT biomaterials, offering improved therapeutic outcomes and the possibility of treating metastatic disease.
• Further studies are warranted to optimize RT doses and elucidate the immune cell populations involved in SRB-mediated anti-tumor responses.