不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:rWTC-MBTA Vaccine, Alone and Enhanced with Anti-PD1, Elicits Immune Responses against CNS and Peripheral B-Cell Lymphoma.
rWTC-MBTA Vaccine, Alone and Enhanced with Anti-PD1, Elicits Immune Responses against CNS and Peripheral B-Cell Lymphoma.
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中枢神经系统(CNS)淋巴瘤因其侵袭性强、脑部可及性有限以及对常规治疗反应差而难以治疗。本研究在A20 B细胞淋巴瘤模型中评估了rWTC-MBTA疫苗单独使用或联合抗PD1治疗的效果。该疫苗单独使用即可通过触发强烈的固有免疫和适应性免疫应答(包括长期记忆)显著抑制皮下和颅内肿瘤生长并延长生存期。免疫图谱分析揭示了淋巴结和TIL(肿瘤浸润淋巴细胞)随时间变化的动态应答。使用接种疫苗小鼠的淋巴结或脾细胞进行共培养实验显示,肿瘤细胞杀伤增强,IFN-γ和TNF-α水平升高,表明存在淋巴瘤特异性免疫。在颅内模型中,对照小鼠脑内可见密集的肿瘤浸润,而接种疫苗的小鼠肿瘤更为分散,向脑室和脑膜的扩散减少。接种疫苗还使肿瘤微环境向更活跃的抗肿瘤状态转变,表现为PD-1⁺ CD8⁺ T细胞增加。将疫苗与抗PD1联合使用可进一步增强抗肿瘤效果。这些发现表明,rWTC-MBTA可诱导针对CNS和外周淋巴瘤的有效且持久的免疫应答,提供长期保护,并与免疫检查点阻断联合使用时显示出协同获益。
Central nervous system (CNS) lymphomas are difficult to treat due to their aggressive nature, limited brain accessibility, and poor response to conventional therapies.
This study evaluates the rWTC-MBTA vaccine, alone or with anti-PD1 therapy, in A20 B-cell lymphoma models. The vaccine alone significantly inhibits tumor growth and extends survival in both subcutaneous and intracranial settings by triggering strong innate and adaptive immune responses, including long-term memory. Immune profiling reveals dynamic responses in lymph nodes and tumor-infiltrating lymphocytes over time.
Co-culture assays with lymph node or spleen cells from vaccinated mice show enhanced tumor cell killing and increased IFN-γ and TNF-α levels, indicating lymphoma-specific immunity. In the intracranial model, control mice has dense tumor infiltration in the brain, while vaccinated mice exhibit more dispersed tumors with reduced spread to ventricles and meninges.
Vaccination also shifts the tumor microenvironment toward a more active antitumor state, marked by increased PD-1⁺ CD8⁺ T cells. Combining the vaccine with anti-PD1 further enhances antitumor effects.
These findings demonstrate that rWTC-MBTA induces potent and durable immune responses against CNS and peripheral lymphomas, offering long-term protection and showing synergistic benefit when combined with immune checkpoint blockade.
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