下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma.
这项初步研究证明,将LTX-315与过继性T细胞疗法联合使用是可行的,并且这种治疗可以诱导全身免疫反应,从而使原本疾病进展的肉瘤患者病情稳定。
LTX-315是一种溶瘤肽,瘤内注射后可引发局部和全身免疫反应。在本试点试验中,我们采用LTX-315联合过继性T细胞疗法(使用体外扩增的TIL(肿瘤浸润淋巴细胞)治疗转移性软组织肉瘤患者。试验纳入6例经重度预处理的患者并接受LTX-315治疗,其中4例患者继续接受过继性T细胞疗法。总体而言,该治疗被认为是安全的,仅出现预期且可管理的毒性。最佳总体临床反应为疾病稳定208天,在该患者中,我们在血液中检测到肿瘤反应性T细胞,其持续存在直至疾病进展。在3例患者中,证实了针对计算机预测新抗原的T细胞反应。此外,LTX-315注射后,血液中新产生的T细胞克隆被生成并扩增。总之,本试点研究证明,将LTX-315与过继性T细胞疗法联合是可行的,并且该治疗可诱导全身免疫反应,从而使原本疾病进展的肉瘤患者疾病稳定。有必要进一步优化治疗方案以提高临床活性。ClinicalTrials.gov标识符:NCT03725605。
LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma with the combination of LTX-315 and adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated patients were included in the trial and treated with LTX-315 of which four patients proceeded to adoptive T-cell therapy. Overall, the treatment was considered safe with only expected and manageable toxicity. The best overall clinical response was stable disease for 208 days, and in this patient, we detected tumor-reactive T cells in the blood that lasted until disease progression. In three patients T-cell reactivity against in silico predicted neoantigens was demonstrated. Additionally, de novo T-cell clones were generated and expanded in the blood following LTX-315 injections. In conclusion, this pilot study provides proof that it is feasible to combine LTX-315 and adoptive T-cell therapy, and that this treatment can induce systemic immune responses that resulted in stabilization of the disease in sarcoma patients with otherwise progressive disease. Further optimization of the treatment protocol is warranted to increase clinical activity. ClinicalTrials.gov Identifier: NCT03725605.
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