ovalbumin and Leukemia--Radiation-Induced

Activation of APC via CD40-CD40 ligand pathway induces up-regulation of costimulatory molecules such as B7 and production of IL-12. Interaction between B7 on APC and CD28 on naive T cells is necessary for priming the T cells. On the other hand, interaction between B7 on APC and CTLA-4 on activated T cells transduces a negative regulatory signal to the activated T cells. In the present study, we attempted to generate tumor-specific CTL by s.c. administration of antigenic peptides encapsulated in multilamellar liposomes (liposomal peptide vaccine) with anti-CD40 mAb and/or anti-CTLA-4 mAb. Liposomal OVA257-264 and anti-CD40 mAb or anti-CTLA-4 mAb were administrated to C57BL/6 mice and the splenocytes were cocultured with OVA257-264 for 4 days. The splenic CD8+ T cells showed a significant cytotoxicity against EL4 cells transfected with cDNA of OVA. In addition, administration of both anti-CD40 and anti-CTLA-4 mAb enhanced the CTL responses. Considerable CTL responses were induced in MHC class II deficient mice by the same procedure. This finding indicated that CTL responses could be generated even in the absence of Th cells. When BALB/c mice were immunized with pRL1a peptide that are tumor-associated Ag of RLmale symbol1 leukemia cells using the same procedure, significant CTL responses were induced and prolonged survival of the BALB/c mice was observed following RLmale symbol1 inoculation. These results demonstrate that anti-CD40 mAb and anti-CTLA-4 mAb function as immunomodulators and may be applicable to specific cancer immunotherapy with antitumor peptide vaccine.

Topics: Abatacept; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Cancer Vaccines; CD40 Antigens; CTLA-4 Antigen; Cytotoxicity, Immunologic; Drug Combinations; Drug Synergism; Female; Immunoconjugates; Injections, Subcutaneous; Leukemia, Radiation-Induced; Liposomes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Neoplasm Transplantation; Ovalbumin; Peptide Fragments; Survival Analysis; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; T-Lymphocytopenia, Idiopathic CD4-Positive; Tumor Cells, Cultured

Antigen-specific immune T lymphocytes of male C57BL/6 mice were enriched in vitro on monolayers of antigen-pulsed syngeneic macrophages. The cells were treated in vitro with RadLV and inoculated intrathymically into irradiated female C56BL/6 animals. Thymomas arising in the inoculated recipients were characterized as donor- (male) type according to their karyotype. In vivo and in vitro cell lines were established from the primary lymphomas, two of which (designated ROT/6.1 and ROT/6.2) were capable of providing antigen- (carrier) specific help in normal or preimmunized mice. None of the lymphomas could induce antigen-specific DTH reaction. Five months after their establishment, ROT/6.2 alone retained its carrier specificity. ROT/6.2 consisted mainly of Lyt-1+ cells, whereas the ROT/6.1 population was more heterogeneous and contained Lyt-1+, Lyt-2+, and Lyt-3+ cells. The carrier specificity of the latter may have been lost due to selection against the specific helper cells during prolonged passages.

Topics: Animals; Antigens, Ly; Cell Line; Cell Transformation, Viral; Dinitrobenzenes; Epitopes; Female; Genetic Carrier Screening; Hypersensitivity, Delayed; Leukemia Virus, Murine; Leukemia, Experimental; Leukemia, Radiation-Induced; Male; Mice; Mice, Inbred C57BL; Ovalbumin; T-Lymphocytes; Thymoma