Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors.
We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2). The leukemia-bearing group received an intravenous injection of 10 million spleen cells (donor lymphocyte infusions) from unvaccinated (Group 3) and TAA/ecdCD40L-vaccinated (Group 4) syngeneic mice 3 days after completion of the TBI and TCDBMT. Groups 3 and 4 mice received three additional sc vaccinations at 7-day intervals with the TAA/ecdCD40L vaccine, in which the TAA was taken from the junctional peptide of the P210bcr-Abl protein. The survival of Groups 3 and 4 mice was significantly longer than that in Groups 1 and 2 mice. Vaccinated mice from Group 4, which developed complete responses, survived up to 350 days post-injection of the leukemia cells without any evidence of leukemia regrowth.
Han
T H
TH
Department of Genetic Therapy, Sydney Kimmel Cancer Center, San Diego, CA, USA.
Tang
Y
Y
Park
Y H
YH
Maynard
J
J
Li
P
P
Akbulut
H
H
Petersen
L
L
Deisseroth
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D023201:CD40 Ligand / Q000008:administration & dosage / Q000235:genetics; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D016313:Genes, abl; D007117:Immunization, Secondary; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D014916:Whole-Body Irradiation
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017931:DNA Primers; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand