Intratumor CpG-oligodeoxynucleotide injection induces protective antitumor T cell immunity.
Tumor cells are typically poorly immunogenic. The same mechanisms that evolved to avoid the induction of immune responses against self tissues, and, hence, autoimmune disease, also have to be overcome for immune therapy of cancer. Toll-like receptor-activating microbial products such as CpG motif containing DNA are among the primary stimuli that the immune system uses to distinguish between infectious nonself (that is to be attacked) and noninfectious self (that must not be attacked). We tested in a murine RMA lymphoma/C57BL/6 model whether providing the infectious nonself context in a tumor-by injecting CpG-oligodeoxynucleotides directly into the tumor-would elicit a protective antitumor response. Complete remission of established solid tumors was achieved in immune competent mice, but not in T cell/B cell-deficient RAG-1 knockout mice. Intratumor injection of CpG-oligodeoxynucleotides was shown to induce a tumor-specific CD4(+) and CD8(+) T cell response of the type 1 effector class, and T cells adoptively transferred the protection to RAG-1 knockout mice. The data show that intratumor injection of CpG-oligodeoxynucleotides is a promising strategy for rendering tumors immunogenic.
Lonsdorf
Anke S
AS
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Kuekrek
Haydar
H
Stern
Britta V
BV
Boehm
Bernhard O
BO
Lehmann
Paul V
PV
Tary-Lehmann
Magdalena
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides