Background: Tumor cell-derived exosomes (TEXs) have been widely used to induce antitumor immune responses in animal models and clinical trials. Similarly, leukemia cell-derived exosomes (LEXs) can induce antileukemia immune responses in animal models. However, the antileukemia immunity induced by LEXs is less effective, which may be due to an inadequate costimulatory capacity.

Methods: In this study, we transduced L1210 leukemia cells with a lentiviral vector encoding two B7 costimulatory molecules (CD80, CD86) and obtained LEXs that highly expressed CD80 and CD86. The antileukemia immune response derived from these LEXs was examined in vitro and in vivo in animal models.

Results: We found that B7 gene-modified LEXs, including LEX-CD80, LEX-CD86, and LEX-8086, could significantly boost the expression of CD80 and CD86 in dendritic cells (DCs) and promote the secretion of functional cytokines such as TNF-α and IL-12. Moreover, these B7 gene-modified LEXs, particularly LEX-CD8086, could effectively induce CD4⁺ T cell proliferation, Th1 cytokine secretion, and an antigen-specific anti-leukemia cytotoxic T lymphocyte (CTL) response. Additional animal studies indicated that immunization with B7 gene-modified LEXs, in particular LEX-CD8086, could significantly retard tumor growth compared to the control LEXnull group.

Conclusions: This study sheds light on the feasibility of obtaining LEXs that overexpress costimulatory molecules via genetically modified leukemia cells, thereby enhancing their anti-leukemia immunity and providing a potential therapeutic strategy that contributes to leukemia immunotherapy.

背景：肿瘤细胞衍生的外来体（TEXs）已被广泛用于在动物模型和临床试验中诱导抗肿瘤免疫反应。同样，白血病细胞衍生的外来体（LEXs）可以在动物模型中诱导抗白血病免疫反应。但是，LEXs诱导的抗白血病免疫效果较差，这可能是由于共刺激能力不足所致。

方法：在这项研究中，我们用编码两个B7共刺激分子（CD80，CD86）的慢病毒载体转导了L1210白血病细胞，并获得了高表达CD80和CD86的LEX。在动物模型的体内和体外检查了源自这些LEX的抗白血病免疫反应。

结果：我们发现B7基因修饰的LEXs，包括LEX-CD80，LEX-CD86和LEX-8086，可以显着增强树突状细胞（DC）中CD80和CD86的表达，并促进功能性细胞因子（如TNF）的分泌-α和IL-12。此外，这些B7基因修饰的LEX，尤其是LEX-CD8086，可以有效诱导CD4 ⁺ T细胞增殖，Th1细胞因子分泌和抗原特异性抗白血病细胞毒性T淋巴细胞（CTL）反应。额外的动物研究表明，与对照组LEXnull组相比，用B7基因修饰的LEXs（尤其是LEX-CD8086）免疫可显着延缓肿瘤的生长。

结论：这项研究揭示了通过基因修饰的白血病细胞获得过表达共刺激分子的LEXs的可行性，从而增强其抗白血病免疫力，并提供了有助于白血病免疫疗法的潜在治疗策略。