Combination immunotherapy and photodynamic therapy for cancer

Abstract

Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

Conjugation of cRGD Peptide to Chlorophyll a Based Photosensitizer (HPPH) Alters Its Pharmacokinetics with Enhanced Tumor-Imaging and Photosensitizing (PDT) Efficacy

“…13 To overcome the difficulties in using large proteins and antibodies as targeting vehicles, 14 there have been efforts to use smaller peptides as targeting vehicles. 15 These peptides recognize fairly specific receptors that are over-expressed on certain tumor cells.…”

Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

“…Although PDT was discovered in the field of microbiology over 100 years ago [85] , up to now PDT has been studied and applied mainly as anticancer treatment. The discovery of antibiotics in 1940s revolutionized the treatment of infectious disease, limiting the development of other potential alternative anti-microbial treatments like PDT.…”