Optimizing In Situ Vaccination During Radiotherapy

Abstract

Effective in situ cancer vaccines require both a means of tumor cell death and a source of adjuvant to activate local dendritic cells. Studies have shown that the use of radiotherapy (RT) to induce tumor cell death and anti-CD40 to activate dendritic cells can result in in situ vaccination in animal models. Here, investigations are carried out on potential strategies to enhance such in situ vaccination. Strategies investigated include the use of smart immunogenic biomaterials (IBM) loaded with anti-CD40 in different tumor types including immunologically cold tumors like pancreatic and prostate tumors. The use of downstream checkpoint inhibitors to further boost such in situ vaccination is also examined. Results indicate that the use of IBM to deliver the anti-CD40 significantly enhances the effectiveness of in situ vaccination with anti-CD40 compared with direct injection in pancreatic and prostate cancers (p < 0.001 and p < 0.0001, respectively). This finding is consistent with significant increase in infiltration of antigen-presenting cells in the treated tumor, and significant increase in the infiltration of CD8+ cytotoxic T lymphocyte into distant untreated tumors. Moreover, in situ vaccination with IBM is consistently observed across different tumor types. Meanwhile, the addition of downstream immune checkpoint inhibitors further enhances overall survival when using the IBM approach. Overall, the findings highlight potential avenues for enhancing in situ vaccination when combining radiotherapy with anti-CD40.

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination

“…Altogether, the results demonstrate major 5B summarizes tumor control and survival of pancreatic cancer when treated with LIFE SRB loaded with titanium oxide and anti-CD40 with and without radiation versus radiation alone [28]. These studies, as reflected in Figures 4 and 5, corroborate the immune-mediated response and show significant regression of both local treated pancreatic tumors and untreated contralateral tumor, representing metastasis, when using RT in combination with either seed-type (Figure 4) or LIFE gel-type (Figure 5) SRB compared to when treating with RT or RT with anti-CD40 alone [30]. Studies also show that the use of SRB is immunogenic (Figure 4C), significantly enhancing infiltration of APCs that are crucial for priming metastatic tumor kill [30,31].…”

“…In situ (intra-tumoral) vaccination with SRB technology may help overcome immunosuppression due to the sustained localization of the immunoadjuvant and simultaneous presence of RT-generated neoantigens in the tumor microenvironment. The use of immunoadjuvants, such as anti-CD40, may increase the activation or maturation of antigen presenting cells that pick-up the neoantigens [ 28 , 30 ]. Delivering immunoadjuvants with SRBs may also increase retention within the tumor, substantially minimizing systemic/overlapping toxicities which are currently a limitation with other approaches [ 30 ].…”

“…The use of immunoadjuvants, such as anti-CD40, may increase the activation or maturation of antigen presenting cells that pick-up the neoantigens [ 28 , 30 ]. Delivering immunoadjuvants with SRBs may also increase retention within the tumor, substantially minimizing systemic/overlapping toxicities which are currently a limitation with other approaches [ 30 ].…”

“…The images demonstrate superior sustained presence of antibody when administered with SRB versus direct injection, showing greater presence up to 13 days post-administration. ( B ) Scatter plots of percent volume change of treated and abscopal tumors when treated with IGRT of 5 Gy was given in combination with either direct injection of anti-CD40 or seed-type SRB loaded with the same [ 30 ]. ( C ) Bar graph of the average fluorescent intensity of immunofluorescence-stained prostate cancer tissue treated with mouse CD11b+ antibody administered intratumorally vs. via smart radiotherapy biomaterials (SRB) at posttreatment day 7 [ 31 ].…”

Polydopamine Nanomaterials for Overcoming Current Challenges in Cancer Treatment

“…Au-coated PDA nanoparticles can advance applications in the field of image-guided radiation therapy as Au is known as both a radiosensitizer and an imaging contrast agent due to its unique optical properties, surface plasmon resonance properties, and photo-electric effect properties, which open up a strong possibility to apply Au-coated PDA nanoparticles in image-guided combined immuno and radiation therapy to treat cancer efficiently with minimum side effects [ 75 , 115 ]. Image-guided combined-radiation therapy and immunotherapy using PDA nanoparticles may offer maximal control of local and metastatic cancerous lesions while sparing healthy tissue [ 116 , 117 ]. Taken together, there are plenty of research opportunities regarding the potential of using PDA in immunotherapy and radiation therapy that have not been explored yet.…”