Therapeutic In Situ Cancer Vaccine Using Pulsed Stereotactic Body Radiotherapy—A Translational Model

Abstract

Both radiation and cancer therapeutic vaccine research are more than 100 years old, and their potential is likely underexplored. Antiangiogenics, nanoparticle targeting, and immune modulators are some other established anticancer therapies. In the meantime, immunotherapy usage is gaining momentum in clinical applications. This article proposes the concept of a pulsed/intermittent/cyclical endothelial-sparing single-dose in situ vaccination (ISVRT) schedule distinguishable from the standard therapeutic stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) plans. This ISVRT schedule can repeatedly generate tumor-specific neoantigens and epitopes for primary and immune modulation effects, augment supplementary immune enhancement techniques, activate long-term memory cells, avoid extracellular matrix fibrosis, and essentially synchronize with the vascular normalized immunity cycle. The core mechanisms of ISVRT impacting in situ vaccination would be optimizing cascading antigenicity and adjuvanticity. The present proposed hypothesis can be validated using the algorithm presented. The indications for the proposed concept are locally progressing/metastatic cancers that have failed standard therapies. Immunotherapy/targeted therapy, chemotherapy, antiangiogenics, and vascular–lymphatic normalization are integral to such an approach.