Development of photodynamic therapy regimens that control primary tumor growth and inhibit secondary disease.
Effective therapy for advanced cancer often requires treatment of both primary tumors and systemic disease that may not be apparent at initial diagnosis. Numerous studies have shown that stimulation of the host immune system can result in the generation of anti-tumor immune responses capable of controlling metastatic tumor growth. Thus, there is interest in the development of combination therapies that both control primary tumor growth and stimulate anti-tumor immunity for control of metastatic disease and subsequent tumor growth. Photodynamic therapy (PDT) is an FDA-approved anticancer modality that has been shown to enhance anti-tumor immunity. Augmentation of anti-tumor immunity by PDT is regimen dependent, and PDT regimens that enhance anti-tumor immunity have been defined. Unfortunately, these regimens have limited ability to control primary tumor growth. Therefore, a two-step combination therapy was devised in which a tumor-controlling PDT regimen was combined with an immune-enhancing PDT regimen. To determine whether the two-step combination therapy enhanced anti-tumor immunity, resistance to subsequent tumor challenge and T cell activation and function was measured. The ability to control distant disease was also determined. The results showed that the novel combination therapy stimulated anti-tumor immunity while retaining the ability to inhibit primary tumor growth of both murine colon (Colon26-HA) and mammary (4T1) carcinomas. The combination therapy resulted in enhanced tumor-specific T cell activation and controlled metastatic tumor growth. These results suggest that PDT may be an effective adjuvant for therapies that fail to stimulate the host anti-tumor immune response.
Department of Cell Stress Biology, PDT Center, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY, 14263, USA.
Madeeha
M
Shams
Barbara
B
Owczarczak
Patricia
P
Manderscheid-Kern
David A
DA
Bellnier
Sandra O
SO
Gollnick
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D005260:Female; D008213:Lymphocyte Activation; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011897:Random Allocation; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D017323:Dihematoporphyrin Ether