Chen Xinchun, Zeng Yi, Li Gang, Larmonier Nicolas, Graner Michael W, Katsanis Emmanuel
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona 85724-5073, USA.
Biol Blood Marrow Transplant. 2006 Mar;12(3):275-83. doi: 10.1016/j.bbmt.2006.01.001.
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.
我们曾报道富含伴侣蛋白的细胞裂解物（CRCL）在免疫活性小鼠中是一种有效的抗癌疫苗。在本研究中，我们探讨了CRCL在同基因造血细胞移植（HCT）背景下治疗已存在的白血病的治疗适用性。我们的结果表明，与接受来自未免疫供体的HCT的动物相比，接受来自12B1肿瘤CRCL免疫供体的同基因HCT的小鼠肿瘤生长显著延迟。与未进行移植后疫苗接种的免疫HCT相比，免疫HCT后进行CRCL免疫进一步阻碍了肿瘤生长。免疫反应的强度与体内观察到的抗肿瘤效果一致。在存活小鼠的对侧腹股沟用12B1或A20细胞再次攻击证实，小鼠已对12B1肿瘤细胞产生了长期的肿瘤特异性免疫。此外，我们记录到T细胞和自然杀伤细胞均对CRCL疫苗接种的抗肿瘤作用有贡献，因为任一亚群的耗竭都会阻碍肿瘤生长延迟。因此，我们的结果表明CRCL是一种有前景的疫苗，能够产生特异性免疫反应。这种抗肿瘤免疫可以通过HCT有效地转移到宿主，并在HCT后通过额外的肿瘤CRCL免疫进一步增强。
