Therapeutic vaccination against a murine lymphoma by intratumoral injection of a cationic anticancer peptide.
Cationic antimicrobial peptides (CAPs) exhibit promising anticancer activities. In the present study, we have examined the in vivo antitumoral effects of a 9-mer peptide, LTX-302, which is derived from the CAP bovine lactoferricin (LfcinB). A20 B cell lymphomas of BALB/c origin were established by subcutaneous inoculation in syngeneic mice. Intratumoral LTX-302 injection resulted in tumor necrosis and infiltration of inflammatory cells followed by complete regression of the tumors in the majority of the animals. This effect was T cell dependent, since the intervention was inefficient in nude mice. Successfully treated mice were protected against rechallenge with A20 cells, but not against Meth A sarcoma cells. Tumor resistance could be adoptively transferred with spleen cells from LTX-302-treated mice. Resistance was abrogated by depletion of T lymphocytes, or either the CD4(+) or CD8(+) T cell subsets. Taken together, these data suggest that LTX-302 treatment induced long-term, specific cellular immunity against the A20 lymphoma and that both CD4(+) and CD8(+) T cells were required. Thus, intratumoral administration of lytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against cancer.
Berge
Gerd
G
Tumor Biology Research Group, IMB, University of Tromsø, Tromsø, Norway.
Eliassen
Liv Tone
LT
Camilio
Ketil Andre
KA
Bartnes
Kristian
K
Sveinbjørnsson
Baldur
B
Rekdal
Oystein
O
D019264:Adoptive Transfer; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000737:chemistry; D019496:Cancer Vaccines; D002417:Cattle; D045744:Cell Line, Tumor; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D019496:Cancer Vaccines; D024243:HMGB1 Protein; D010446:Peptide Fragments; C082171:lactoferricin B; D007781:Lactoferrin