Peritransplantation vaccination with chaperone-rich cell lysate induces antileukemia immunity.
We have reported that chaperone-rich cell lysate (CRCL) is an effective anticancer vaccine in immunocompetent mice. In this study, we explored the therapeutic applicability of CRCL in the context of syngeneic hematopoietic cell transplantation (HCT) to treat preexisting leukemia. Our results demonstrate that tumor growth is significantly delayed in mice receiving syngeneic HCT from 12B1 tumor CRCL-immunized donors compared with animals receiving HCT from nonimmunized donors. CRCL immunization after immune HCT further hindered tumor growth when compared with immune HCT without posttransplantation vaccination. The magnitude of the immune response was consistent with the antitumor effects observed in vivo. Rechallenge of surviving mice with 12B1 or A20 cells in opposite groins confirmed that mice had developed long-term tumor-specific immunity against 12B1 tumor cells. In addition, we documented that both T cells and natural killer cells contributed to the antitumor effect of CRCL vaccination, because depletion of either subset hampered tumor growth delay. Thus, our results indicate that CRCL is a promising vaccine capable of generating specific immune responses. This antitumor immunity can be effectively transferred to a host via HCT and further enhanced after HCT with additional tumor CRCL immunizations.
Chen
Xinchun
X
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona 85724-5073, USA.
Zeng
Yi
Y
Li
Gang
G
Larmonier
Nicolas
N
Graner
Michael W
MW
Katsanis
Emmanuel
E
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002457:Cell Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D014185:Transplantation, Isogeneic
D019496:Cancer Vaccines; D002457:Cell Extracts; D018832:Molecular Chaperones