Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen

Abstract

Background:Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70).Methods:Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-β (TGF-β) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival.Results:Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-β levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without.Conclusion:Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion.

Elimination of primary tumours and control of metastasis with rationally designed bacteriochlorin photodynamic therapy regimens

“…Only mice with CT26.CL25 tumours expressing the tumour antigen b-galactosidase could be cured and acquired immune memory [26]. Cures in BALB/c mice bearing CT26 tumours with verteporfin-PDT required the preliminary administration of cyclophosphamide, an anti-cancer drug that selectively depletes Treg cells in mice, and this combination produces a greater local oedema than PDT alone [27]. Vascular-PDT with WST11 resulted in cure of 70% BALB/c and 19% BALB/c nude mice with implanted CT26 tumours [21].…”

Photodynamic therapy of cancer — Challenges of multidrug resistance

“…92 Reginato et al showed that the depletion of T-regulatory cells could potentiate PDT-mediated immunity. 93 …”

Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model

“…As a result, this model is prone to tumor relapse after VPDT although the tumor itself expresses the tumor antigen gp70. 41 It has been reported that verteporfin-VPDT could achieve tumor-free survival together with an induction of immunological memory (i.e., a complete response) in cell lines that bear a tumor rejection antigen, for example, RIF-1 tumors with EGFP in C3H/HeN mice, P815 tumors with P1A antigen in DBA/2 mice, or with the depletion of Treg cells in J774 tumors in BALB/c mice. 31,42,43 However, when CT26 tumors were treated with verteporfin, a complete response could be achieved only when repetitive low doses of cyclophosphamide were administered to deplete the Treg population.…”

“…31,42,43 However, when CT26 tumors were treated with verteporfin, a complete response could be achieved only when repetitive low doses of cyclophosphamide were administered to deplete the Treg population. 41 Alternatively, an additional foreign antigen, such as b-galactosidase, must be transfected into the tumor cells to strengthen its immunogenicity before the treatment. 45 In contrast, some other PSs (for example, hypericin and WST11 13,30 ) could trigger a complete response in the CT26 tumor model without the aid of extra immunomodulatory agents.…”