Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based vaccines: Therapeutic effect against cervical cancer
Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein-based vaccines: Therapeutic effect against cervical cancer
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DOI：
10.1007/s00262-005-0685-2
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发表时间：
2005-12-01
影响因子：
5.8
通讯作者：
Huang, L
中科院分区：
文献类型：
--
作者：
Cui, ZR;Huang, L
随着许多肿瘤特异性抗原和肿瘤相关抗原的成功鉴定，以及利用完整的肿瘤细胞衍生物作为肿瘤抗原的可能性，迫切需要一个能够递送这些抗原并帮助它们诱导强大而有效的抗肿瘤免疫反应的系统和/或佐剂。此前，我们曾报道，来自人乳头瘤病毒(HPV)16E7蛋白的MHC I类限制性多肽表位，当被整合到临床证明安全的LPD(脂质体-聚阳离子-DNA)颗粒中时，能够有效地根除小鼠体内建立的肿瘤。宫颈癌是全球女性中第二常见的癌症。HPV感染显然与这种癌症有关。基于HPV早期(E)基因产物的疫苗可以有效地控制它。然而，除了表位疫苗有许多局限性外，尤其是在人类体内，使用表位作为抗原，使我们无法充分描述LPD作为疫苗载体和/或佐剂诱导的免疫反应。在本研究中，我们首先以HPV16E7蛋白作为抗原，证明了LPD作为疫苗载体和佐剂诱导了强大的细胞和抗体免疫反应。然后，我们展示了LPD颗粒与野生型HPV16E7蛋白或潜在更安全的突变体相结合的免疫诱导了强烈的免疫反应，导致在小鼠中建立的宫颈癌模型肿瘤完全消退。LPD可作为多种抗原的有效疫苗载体和佐剂。
With the successful identification of many tumor-specific antigens, tumor-associated antigens, and the potential of using unfractioned tumor cell derivatives as tumor antigens, a system and/or adjuvant that can deliver these antigens and help them to induce strong and effective anti-tumor immune responses is greatly needed. Previously, we reported that a MHC class I-restricted peptide epitope derived from human papillomavirus (HPV) 16 E7 protein, when incorporated into a clinically proven safe LPD (liposome-polycation-DNA) particle, was able to effectively eradicate tumors established in mice. Cervical cancer is the second most common cancer among women worldwide. HPV infection is clearly linked to this cancer. Vaccines based on the early (E) gene products of HPV could be effective in controlling it. However, besides the fact that epitope vaccines have many limitations particularly, concerning the diverse HLAs in humans, the use of the epitope as an antigen prevented us from fully characterizing the immune responses induced by the LPD as a vaccine carrier and/or adjuvant in previous studies. In the present study, by using the HPV 16 E7 protein as an antigen, we first showed that LPD, as a vaccine carrier and adjuvant induced strong and robust immune responses, both cellular and antibody. We then showed that immunization with LPD particles incorporated with either the wild type HPV 16 E7 protein or a potentially safer mutant induced strong immune responses that caused complete regressions of a model cervical cancer tumor established in murines. LPD could be a potent vaccine carrier and/or adjuvant for many antigens.