Immunization against endogenous retroviral tumor-associated antigens.
Immunization against endogenous retroviral tumor-associated antigens.
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针对内源性逆转录病毒肿瘤相关抗原的免疫。
作者：
M. Kershaw;C. Hsu;W. Mondesire;L. L. Parker;G. Wang;W. Overwijk;R. Lapointe;J. C. Yang;R. Wang;N. Restifo;P. Hwu
内源性逆转录病毒基因产物已在一些人类肿瘤中发现，因此，可作为免疫治疗方法的抗原。最近发现小鼠结直肠癌CT 26和黑色素瘤B16分别表达内源性逆转录病毒基因产物gp 70和p15 E，它们可以作为T细胞识别的抗原。然而，迄今为止，还没有证据表明使用内源性逆转录病毒蛋白治疗肿瘤。在这项研究中，我们证明了用编码gp 70 H2-L（d）限制性最小决定簇的重组牛痘免疫的小鼠免受CT 26肿瘤攻击。来自用牛痘gp 70免疫的小鼠的脾细胞响应gp 70肽脉冲刺激物特异性地分泌IFN-γ。虽然这种策略可以防止随后的肿瘤攻击，但它对已建立的肿瘤无效。因此，为了研究已建立的CT 26或B16肺转移的治疗，用用gp 70或p15 E肽脉冲的培养的树突状细胞（DC）处理小鼠。显著抑制已建立的肺转移需要用经CD 40配体预处理的肽脉冲的DC免疫，已证明所述肽脉冲的DC增加DC的T细胞刺激活性。对内源性逆转录病毒肿瘤抗原免疫的能力可能与诱导某些人类癌症的抗肿瘤免疫有关。
Endogenous retroviral gene products have been found in some human tumors, and therefore, may serve as antigens for immunotherapy approaches. The murine colorectal carcinoma CT26 and melanoma B16 have recently been found to express the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there has been no demonstration of tumor treatment using an endogenous retroviral protein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L(d)-restricted minimal determinant were protected from CT26 tumor challenge. Splenocytes from mice immunized with vaccinia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to investigate the treatment of established CT26 or B16 lung metastases, mice were treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E peptide. Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs. The ability to immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers.
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影响因子：
32.4
作者：
Slansky, JE;Rattis, FM;Pardoll, DM
通讯作者：
Pardoll, DM
DOI：
10.1073/pnas.93.18.9730
发表时间：
1996-09-03
影响因子：
11.1
作者：
Huang, AYC;Gulden, PH;Jaffee, EM
通讯作者：
Jaffee, EM
影响因子：
4.4
作者：
Mark Gavin;Mark J. Gilbert;Stanley R. Riddell;Philip D. Greenberg;Michael J. Bevan
通讯作者：
Mark Gavin;Mark J. Gilbert;Stanley R. Riddell;Philip D. Greenberg;Michael J. Bevan
来自人类结肠肿瘤和粘膜的 mRNA，与内源 A 型逆转录病毒的 pol 基因相关。
DOI：
10.1016/s0006-291x(86)80286-8
发表时间：
1986
影响因子：
3.1
作者：
Moshier,JA;Luk,GD;Huang,RC
通讯作者：
Huang,RC
影响因子：
4.4
作者：
M. Roy;T. Waldschmidt;A. Aruffo;J. Ledbetter;R. Noelle
通讯作者：
M. Roy;T. Waldschmidt;A. Aruffo;J. Ledbetter;R. Noelle