Calreticulin as Cancer Treatment Adjuvant: Combination with Photodynamic Therapy and Photodynamic Therapy-Generated Vaccines

Abstract

Calreticulin is recognized as one of the pivotal damage-associated molecular pattern molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT). The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse) was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT-vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT-vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor response elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

Mreg Activity in Tumor Response to Photodynamic Therapy and Photodynamic Therapy-Generated Cancer Vaccines

“…The photosensitizer Temoporfin (Foscan) was provided by Biolitec Research GmbH (Jena, Germany). Other details of light delivery were described earlier [32]. At chosen intervals after PDT, some mice received 0.1 mg i.v.…”

“…The cells were then collected, exposed to X-rays (60 Gy), and delivered (2 × 10 7 per mouse) by peritumoral injection. Further details of experimental protocol were specified elsewhere [24,32]. Cyclophosphamide (Sigma) administration, 50 mg/kg dose i.p.…”

Programmed cell removal biomarkers calreticulin and CD47 implicated in oral lichen planus

“…Currently, there are developments in both CD47 and CRT antibodies mainly for cancer therapy (Ho et al , ; Korbelik et al , ; Xiao et al , ). Human clinical trials of the anti‐CD47 cancer therapy begun in 2014, aiming at causing the immune system to wage a two‐pronged attack on cancer through both macrophages and T cells.…”

Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death

“…In this matter, Korbelik et al evaluated the effect of exogenously added CRT for improving the antitumor effect mediated by PDT [277]. They showed that antitumor immune response, prompted via PDT or PDT-generated vaccines, could be enhanced by externally added CRT and can be an operative adjuvant for cancer therapy with PDT [287].…”