Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine.
Cancer vaccines composed of tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) are currently being clinically evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines, a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the tumor cell surface was investigated. The intent was to enhance antigen presentation by increasing interactions between the tumor cell lines in the vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the patient's Langerhans cells residing within the intradermal injection site. B16.F10 cells engineered to express either membrane-bound or secreted GM-CSF were compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on the tumor cell surface retarded growth and induced protective immunity to subsequent wild-type tumor challenge more effectively than tumor cells secreting GM-CSF. Vaccination with irradiated mbGM-CSF B16.F10 also provided strong protection from wild-type tumor challenge, improved therapeutic effects against established tumors, and retarded lung metastases. These results demonstrate that mbGM-CSF B16.F10 cells can induce strong systemic immunity that protects against and therapeutically treats B16.F10 melanoma more effectively than analogous vaccines containing only secreted GM-CSF. These data warrant further development and clinical testing of mbGM-CSF tumor cell vaccines.
Yei
S
S
Division of Cancer, The Immune Response Corporation, 5935 Darwin Court, Carlsbad, CA 92008, USA.
Bartholomew
R M
RM
Pezzoli
P
P
Gutierrez
A
A
Gouveia
E
E
Bassett
D
D
Soo Hoo
W
W
Carlo
D J
DJ
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D016867:Immunocompromised Host; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor