Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy1
Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy1
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基于树突状细胞的异种抗原疫苗接种用于前列腺癌免疫治疗1
作者：
L. Fong;D. Brockstedt;C. Benike;Jami K. Breen;G. Strang;C. Ruegg;E. Engleman
许多肿瘤相关Ags代表免疫原性较差的组织分化Ags。其免疫原性弱可能是由于对自身ags的免疫耐受所致。前列腺酸性磷酸酶（PAP）就是这样一种抗原，在正常和恶性前列腺组织中均有表达。我们之前已经证明PAP在啮齿动物模型中具有免疫原性。然而，只有当使用PAP异种同源物作为免疫原时，才能观察到前列腺特异性自身免疫的产生。为了探索异种抗原免疫在癌症患者中的潜在作用，我们进行了一项I期临床试验，使用重组小鼠PAP脉冲树突状细胞作为肿瘤疫苗。21名转移性前列腺癌患者每月接受两次载异种抗原树突状细胞疫苗接种，治疗相关副作用最小。所有患者免疫后均对小鼠PAP产生T细胞免疫。21例患者中有11例也对同源自体抗原产生T细胞增殖反应。这些反应与ag特异性IFN-γ和/或TNF-α分泌有关，但与IL-4无关，与诱导Th1免疫一致。最后，21例患者中有6例先前进展的前列腺癌临床稳定。这6例患者在接种疫苗后均对人类PAP产生T细胞免疫。这些结果表明，异种抗原免疫可以打破人类对自身抗原的耐受性，从而产生临床显着的抗肿瘤作用。
Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFN-γ and/or TNF-α secretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect.
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前列腺酸性磷酸酶免疫诱导组织特异性自身免疫性前列腺炎：对前列腺癌免疫治疗的影响。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fong,L;Ruegg,CL;Brockstedt,D;Engleman,EG;Laus,R
通讯作者：
Laus,R
DOI：
10.1073/pnas.96.10.5710
发表时间：
1999-05-11
影响因子：
11.1
作者：
Slovin, SF;Ragupathi, G;Scher, HI
通讯作者：
Scher, HI
高浓度的免疫显性天然肽诱导 T 细胞无反应性，并伴随着 IL-10 的产生和 JNK 活性的阻断。
DOI：
10.1006/cimm.1998.1342
发表时间：
1998
期刊：
Cellular immunology.
影响因子：
--
作者：
Chou,YK;Robey,I;Woody,CN;Li,W;Offner,H;Vandenbark,AA;Davey,MP
通讯作者：
Davey,MP
影响因子：
7
作者：
C. Yee;S. Riddell;P. Greenberg
通讯作者：
C. Yee;S. Riddell;P. Greenberg
影响因子：
4.4
作者：
A. Mehta-Damani;S. Markowicz;E. Engleman
通讯作者：
A. Mehta-Damani;S. Markowicz;E. Engleman