CpG oligodeoxynucleotide-induced immunity prevents growth of germinal center-derived B lymphoma cells.
Therapeutic efficacy of CpG oligodeoxynucleotide (ODN) ISS 1018 was tested in a murine B cell lymphoma model. Previous studies showed that the B lymphoma cells of SJL mice stimulate vigorous proliferation of host CD4(+) TH cells that is unaccompanied by development of tumor-specific CTL. In the presence of ISS 1018, however, tumor cells stimulated high levels of CTL activity in vitro, and this cytotoxic activity was inhibited when anti-IL-12 mAb was added to the cultures. Tumor cells pre-incubated with ISS 1018 were also able to generate CTL without addition of exogenous ODN, and FACS analysis revealed that following incubation with ISS 1018 for 24 h, tumor cells exhibited upregulation of MHC I, MHC II, and co-stimulatory molecule CD80. Finally, tumor-injected mice treated with ISS 1018 showed significantly less growth of tumor cells in lymph nodes and spleen, and exhibited prolonged survival compared to mice treated with a control ODN. The documented effects of CpG ODNs to stimulate cytokines, such as IL-12, from antigen presenting cells, and to upregulate expression of MHC Class I and Class II, as well as co-stimulatory molecules on tumor cells, are also the likely mechanisms by which CTL are generated by ISS 1018 in the SJL B cell lymphoma model.
Ponzio
Nicholas M
NM
Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, NJ 07107, United States. ponzio@umdnj.edu <ponzio@umdnj.edu>
Cutro
Scott
S
Hu
Jessica
J
Marzouk
Atara
A
Marshall
Jason D
JD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D018858:Germinal Center / Q000187:drug effects / Q000473:pathology*; D006649:Histocompatibility Antigens / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006649:Histocompatibility Antigens; D007155:Immunologic Factors; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; C489630:1018 oligonucleotide