Lifileucel Therapy for Metastatic Melanoma: Advancements in Tumor-infiltrating Lymphocyte-based Immunotherapy.

IF 3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Issac V Cherian, Md Mustahidul Islam, Mamta Bishnoi, Sakshi Priya, Balak Das Kurmi, Sourabh Koshey, Preeti Patel
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Abstract

Metastatic melanoma is an aggressive malignancy with limited treatment options at advanced stages. Lifileucel, an FDA-approved autologous Tumor-Infiltrating Lymphocyte (TIL) therapy, marks a major advancement in immunotherapy, particularly for patients who fail conventional treatments like immune checkpoint inhibitors and targeted therapies. The mechanism of lifileucel involves the ex vivo expansion of patient-derived TILs to boost immune responses against melanoma cells. These expanded TILs are re-infused into patients, enhancing tumor-specific cytotoxicity and modulating the tumor microenvironment for sustained immune activation. Clinical trials have demonstrated its efficacy, with the overall response rate (ORR) reaching up to 36% in heavily pretreated populations, offering durable responses and improved progression-free survival compared to traditional therapies. The personalized approach of lifileucel, leveraging the patient's own T-cell repertoire, highlights its potential for precision oncology by targeting individual tumor profiles. Its integration with combination therapies, particularly immune checkpoint inhibitors, shows promising synergistic effects, broadening its clinical applicability. In addition to clinical success, the role of lifileucel in influencing the melanogenesis pathway offers insights into optimizing therapeutic strategies for melanoma. Ongoing research focuses on enhancing TIL functionality, overcoming challenges like tumor-induced immune suppression, and extending the applicability of lifileucel to other solid tumors. This breakthrough therapy not only addresses a critical unmet need in melanoma treatment but also represents a paradigm shift toward personalized medicine in oncology. Lifileucel underscores the potential of TILbased approaches to revolutionize cancer care, setting the stage for future advancements in immunotherapy.

转移性黑色素瘤的Lifileucel治疗:肿瘤浸润性淋巴细胞免疫治疗的进展。
转移性黑色素瘤是一种侵袭性恶性肿瘤,晚期治疗选择有限。Lifileucel是一种fda批准的自体肿瘤浸润淋巴细胞(TIL)治疗药物,标志着免疫治疗的重大进步,特别是对于免疫检查点抑制剂和靶向治疗等常规治疗失败的患者。lifileucel的机制涉及患者源性til的体外扩增,以增强对黑色素瘤细胞的免疫反应。这些扩展后的TILs被重新输注到患者体内,增强肿瘤特异性细胞毒性,调节肿瘤微环境,以实现持续的免疫激活。临床试验已经证明了它的有效性,在大量预处理的人群中,总缓解率(ORR)高达36%,与传统疗法相比,提供了持久的缓解和改善的无进展生存期。lifileucel的个性化方法,利用患者自身的t细胞库,突出了其针对个体肿瘤特征的精确肿瘤学潜力。它与联合疗法,特别是免疫检查点抑制剂的结合,显示出有希望的协同作用,扩大了其临床适用性。除了临床成功,lifileucel在影响黑色素形成途径中的作用为优化黑色素瘤的治疗策略提供了见解。正在进行的研究重点是增强TIL功能,克服肿瘤诱导的免疫抑制等挑战,并将lifileucel的适用性扩展到其他实体肿瘤。这一突破性疗法不仅解决了黑色素瘤治疗中一个关键的未满足的需求,而且代表了肿瘤学向个性化医疗的范式转变。Lifileucel强调了基于till的癌症治疗方法的潜力,为未来免疫治疗的进步奠定了基础。
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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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