Tumor cell lysate-pulsed dendritic cells are more effective than TCR Id protein vaccines for active immunotherapy of T cell lymphoma
Tumor cell lysate-pulsed dendritic cells are more effective than TCR Id protein vaccines for active immunotherapy of T cell lymphoma
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DOI：
10.4049/jimmunol.169.9.5227
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发表时间：
2002-11-01
影响因子：
4.4
通讯作者：
Okada, CY
中科院分区：
文献类型：
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作者：
Gatza, E;Okada, CY
TCR ID蛋白与锁孔帽状血蓝蛋白结合(TCR ID：KLH)并注射化学佐剂(QS-21)可诱导针对小鼠T细胞淋巴瘤C6VL的保护性ID特异性免疫反应。然而，基于ID的C6VL免疫治疗在荷瘤小鼠中并未显示出疗效。我们在此报道，与使用QS-21疫苗的TCRID：K1H相比，C6VL裂解冲击树突状细胞(C6VL-DC)疫苗在预防和治疗T细胞淋巴瘤方面显示出更好的疗效。C6VL-DC疫苗激发了强大的肿瘤特异性免疫，保护小鼠免受C6VL的致命攻击，并显著提高了荷瘤小鼠的存活率。通过体外刺激疫苗预置的淋巴细胞，观察到肿瘤特异性增殖和分泌指示Th1型免疫反应的干扰素-γ。过继转移免疫T细胞丰富的淋巴细胞足以保护幼稚的受者免受致命的肿瘤攻击。此外，CD8(+)T细胞是肿瘤保护必不可少的细胞。虽然C6VL-DC和对照疫苗刺激小鼠产生低水平的肿瘤特异性抗体，但抗体水平与疫苗的保护能力无关。因此，肿瘤细胞裂解物冲击的DC疫苗似乎是一种有效的方法，可以产生强大的T细胞介导的针对T细胞恶性肿瘤的免疫反应，而不需要鉴定肿瘤特异性的AGS或患者特异性的ID蛋白表达。
TCR Id protein conjugated to keyhole limpet hemocyanin (KLH) (TCR Id:KLH) and injected with a chemical adjuvant (QS-21) induces a protective, Id-specific immune response against the murine T cell lymphoma, C6VL. However, Id-based immunotherapy of C6VL has not demonstrated therapeutic efficacy in tumor-bearing mice. We report here that C6VL lysate-pulsed dendritic cells (C6VL-DC) vaccines display enhanced efficacy in both the prevention and the therapy of T cell lymphoma compared with TCR Id:KLH with QS-21 vaccines. C6VL-DC vaccines stimulated potent tumor-specific immunity that protected mice against lethal challenge with C6VL and significantly enhanced the survival of tumor-bearing mice. Tumor-specific proliferation and secretion of IFN-gamma indicative of a Th1-type immune response were observed upon ex vivo stimulation of vaccine-primed lymph node cells. Adoptive transfer of immune T cell-enriched lymphocytes was sufficient to protect naive recipients from lethal tumor challenge. Furthermore, CD8(+) T cells were absolutely required for tumor protection. Although C6VL-DC and control vaccines stimulated low levels of tumor-specific Ab production in mice, Ab levels did not correlate with the protective ability of the vaccine. Thus, tumor cell lysate-pulsed DC vaccines appear to be an effective approach to generate potent T cell-mediated immune responses against T, cell malignancies without requiring identification of tumor-specific Ags or patient-specific Id protein expression.