Cellular immune response to an engineered cell-based tumor vaccine at the vaccination site.
The engineered expression of the immune co-stimulatory molecules CD80 and CD137L on the surface of a neuroblastoma cell line converts this tumor into a cell-based cancer vaccine. The mechanism by which this vaccine activates the immune system was investigated by capturing and analyzing immune cells responding to the vaccine cell line embedded in a collagen matrix and injected subcutaneously. The vaccine induced a significant increase in the number of activated CD62L(-) CCR7(-) CD49b(+) CD8 effector memory T cells captured in the matrix. Importantly, vaccine responsive cells could be detected in the vaccine matrix within a matter of days as demonstrated by IFN-gamma production. The substitution of unmodified tumor cells for the vaccine during serial vaccination resulted in a significant decrease in activated T cells present in the matrix, indicating that immune responses at the vaccine site are a dynamic process that must be propagated by continued co-stimulation.
Zhou
Qiang
Q
Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, Children's Hospital of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Johnson
Bryon D
BD
Orentas
Rimas J
RJ
D053330:4-1BB Ligand / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D001672:Biocompatible Materials / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000008:administration & dosage; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004338:Drug Combinations; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology / Q000276:immunology; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D039421:Integrin alpha2 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D007797:Laminin / Q000008:administration & dosage; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000276:immunology*; D011509:Proteoglycans / Q000008:administration & dosage; D000099192:CD69 Antigens
D053330:4-1BB Ligand; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D003094:Collagen; D004338:Drug Combinations; D039421:Integrin alpha2; D019041:L-Selectin; D007797:Laminin; D037181:Lectins, C-Type; D011509:Proteoglycans; D000099192:CD69 Antigens; C059485:matrigel