ELI-002

Phase 2 randomized study of ELI-002 enrolled 135 patients; formal interim analysis of disease-free survival (“DFS”) expected in H1 2025BOSTON, Dec. 03, 2024 (GLOBE NEWSWIRE) -- Elicio Therapeutics, Inc. (Nasdaq: ELTX, “Elicio Therapeutics” or “Elicio”), a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer, today announced the completion of enrollment in the Phase 2 AMPLIFY-7P study (NCT05726864). The randomized Phase 2 study is evaluating a 7-peptide formulation of ELI-002 (ELI-002 7P) in patients with mutant KRAS (“mKRAS”)-driven pancreatic ductal adenocarcinoma (“PDAC”) who are at high risk of relapse following surgery. Elicio previously reported AMPLIFY-7P Phase 1a study results demonstrating a favorable safety profile, robust T-cell responses, antigen spreading and encouraging preliminary DFS data in PDAC patients. “We are pleased to announce the completion of enrollment in our lead ELI-002 Phase 2 AMPLIFY-7P study. The speed of study enrollment exceeded our expectations, reflecting high levels of investigator and patient interest in an off-the-shelf monotherapy treatment option for patients who completed neoadjuvant, perioperative, or adjuvant chemotherapy,” said Christopher Haqq, M.D., Ph.D., Elicio’s Executive Vice President, Head of Research and Development and Chief Medical Officer. “We are now eagerly looking forward to the pre-planned interim data analysis as we continue working to bring this potentially transformative vaccine to cancer patients.” The Phase 2 AMPLIFY-7P study is a multicenter, open-label, randomized trial designed to evaluate the safety, tolerability and efficacy of ELI-002 7P. The trial enrolled a total of 135 PDAC patients, who were randomized 2:1 to receive subcutaneous injections of ELI-002 7P versus standard of care observation. Patients randomized to observation are eligible to cross-over to ELI-002 7P treatment in the event of confirmed disease progression. All patients enrolled in the study had undergone successful (R0/R1) resection of locoregional PDAC (Stages I, II, or III) harboring KRAS mutations—including G12D, G12R, G12V, G12C, G12A, G12S or G13D—and enrollment was agnostic of minimal residual disease (“MRD”) status. These patients are known to remain at high risk of disease recurrence. The primary endpoint of the Phase 2 trial is DFS. Key secondary and exploratory endpoints include serum tumor biomarker responses, overall survival, and vaccine immunogenicity. The first patient to enroll in the Phase 2 study was dosed in January 2024. A formal interim Phase 2 analysis, including DFS, reviewed by the study’s Independent Data Monitoring Committee, is on track for the first half of 2025. Possible outcomes include: (1) successfully achieving pre-specified criteria for reporting primary endpoint analysis; (2) continuing to final DFS analysis, expected in the second half of 2025; or (3) meeting pre-specified criteria for futility. Results from the single-arm Phase 1a portion of AMPLIFY-7P, including translational data highlighting the relationship between vaccine immunogenicity and DFS, were recently presented at the Society for Immunotherapy of Cancer (“SITC”) 2024 Annual Meeting. About Elicio Therapeutics Elicio Therapeutics, Inc. (Nasdaq: ELTX) is a clinical-stage biotechnology company advancing novel immunotherapies to prevent the recurrence of high-prevalence cancers, including mKRAS-positive pancreatic and colorectal cancers. Elicio intends to build on recent clinical successes in the personalized cancer vaccine space to develop effective, off-the-shelf vaccines. Elicio’s Amphiphile (“AMP”) technology aims to enhance the education, activation, and amplification of cancer-specific T cells relative to conventional vaccination strategies, with the goal of promoting durable cancer immunosurveillance in patients. Elicio’s ELI-002 lead program is an off-the-shelf vaccine candidate targeting the most common KRAS mutations, which drive approximately 25% of all solid tumors. ELI-002 is being studied in an ongoing, randomized clinical trial in patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. Elicio’s pipeline includes additional off-the-shelf therapeutic cancer vaccines, including ELI-007 and ELI-008, that target BRAF-driven cancers and p53 hotspot mutations, respectively. For more information, please visit www.elicio.com. About ELI-002 Our lead product candidate, ELI-002, is a structurally novel investigational AMP cancer vaccine that targets cancers that are driven by mutations in the KRAS-gene—a prevalent driver of many human cancers. ELI-002 is comprised of two powerful components that are built with our AMP technology consisting of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant that is available as an off-the-shelf subcutaneous administration. ELI-002 2P (2-peptide formulation) has been studied in the Phase 1 (AMPLIFY-201) trial in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P (7-peptide formulation) is currently being studied in a Phase 1/2 (AMPLIFY-7P) trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations present in 25% of all solid tumors, thereby increasing the potential patient population for ELI-002. About the Amphiphile Platform Our proprietary AMP platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. We believe this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. We believe our AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on preclinical studies. Our AMP platform, originally developed at the Massachusetts Institute of Technology, has broad potential in the cancer space to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships. The AMP platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the local injection site, as it travels to lymphatic tissue. In preclinical models, we have observed lymph node-specific engagement driving immune responses of increased magnitude, function and durability. Cautionary Note on Forward-Looking Statements Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, known as the PSLRA. These include statements regarding Elicio’s planned clinical programs, including planned clinical trials, the potential of Elicio’s product candidates, and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Elicio undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, Elicio’s financial condition, including its anticipated cash runway and ability to obtain the funding necessary to advance the development of ELI-002 and any other future product candidates, and Elicio’s ability to continue as a going concern; Elicio’s plans to develop and commercialize its product candidates, including ELI-002; the timing of initiation of Elicio’s planned clinical trials; the timing of the availability of data from Elicio’s clinical trials, including the timing of the pre-planned formal interim Phase 2 AMPLIFY-7P data analysis in the first half of 2025 and the possible outcomes following such analysis; the timing of any planned investigational new drug application or new drug application; Elicio’s plans to research, develop and commercialize its current and future product candidates; and Elicio’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. New factors emerge from time to time, and it is not possible for us to predict all such factors, nor can we assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. These risks are more fully discussed in the Annual Report on Form 10-K filed with the SEC on March 29, 2024, as amended on April 29, 2024, under the heading “Risk Factors”, and any subsequent reports and other documents filed from time to time with the SEC. Forward-looking statements included in this release are based on information available to Elicio as of the date of this release. Elicio does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this release, except to the extent required by law. Investor Relations Contact Carlo Tanzi, Ph.D.ctanzi@kendallir.com

点击蓝字 关注我们 余玥霖，刘宝瑞（南京大学医学院附属鼓楼医院  肿瘤中心，江苏  南京  210008） 通信作者：刘宝瑞 E-mail ：baoruiliu@nju.edu.cn 通讯作者 刘宝瑞 教授 主任医师，教授，博导 南京大学临床肿瘤研究所所长 南京大学医学院鼓楼医院肿瘤中心主任/免疫治疗中心主任 《中国肿瘤生物治疗杂志》副主编 《肿瘤综合治疗电子杂志》副主编 中国临床肿瘤学会胃癌专委会副主任委员 江苏省抗癌协会整合肿瘤学专委会主任委员 江苏省医师协会肿瘤化疗与生物治疗医师分会主任委员 中国医师奖获得者 江苏省突贡专家 南京大学首届十佳研究生导师 临床重点：难治性肿瘤个体化免疫整合治疗 科研方向：恶性肿瘤个体化与靶向免疫治疗新技术 主持课题：国家自然科学基金重点项目、国际合作重大项目等国家省市课题30余项 【摘要】近年来，随着肿瘤免疫治疗的蓬勃发展，肿瘤疫苗已经由动物实验研究阶段进入临床转化阶段。伴随2024年各大国际肿瘤年会的召开，肿瘤疫苗的众多试验成果也进入了公众视野，引起了人们的广泛关注。肿瘤疫苗又可分为预防性疫苗和治疗性疫苗。本文重点关注肿瘤治疗性疫苗中的信使RNA疫苗、树突状细胞疫苗、合成肽疫苗和病毒载体疫苗，论述2024年度国内外肿瘤治疗性疫苗相关的临床试验，旨在为肿瘤治疗性疫苗未来的发展方向提供思路启迪新思维，开辟新路径。 【关键词】肿瘤治疗性疫苗；肿瘤预防性疫苗；免疫治疗；临床试验 近年来，随着各种组学和生物信息学技术的不断进步，肿瘤疫苗的研发和临床转化已成为最令人瞩目的研究方向。肿瘤疫苗主要分为预防性疫苗和治疗性疫苗。流行病学调查显示，人群罹患传染病或接种疫苗可降低肿瘤发生的风险，接种疫苗可以作为肿瘤高风险人群的预防措施，如乙型病毒性肝炎疫苗已证实对原发性肝癌具有预防作用，人乳头瘤病毒（human papillomavirus，HPV）疫苗能预防宫颈癌，均已上市并得到广泛应用[1]。肿瘤治疗性疫苗的原理是将肿瘤抗原以多种形式，如肿瘤细胞、多肽、表达肿瘤抗原的基因等，注射入患者体内，增强免疫原性，激活人体自身特异性免疫反应，从而达到控制或清除肿瘤的目的[2]。随着2024年美国癌症研究协会（American Association for Cancer Research，AACR）年会、美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会、欧洲肿瘤内科学会年会等重要国际肿瘤会议的召开，更多肿瘤治疗性疫苗的研究成果于大会上公布。本文旨在论述2024年度国内外肿瘤治疗性疫苗相关的临床试验，以期为相关领域的研究奠定理论基础。 1  2024年度肿瘤治疗性疫苗相关临床试验 2024年肿瘤治疗性疫苗相关的临床试验正在有条不紊地开展（表1）。通过国际著名的临床试验注册中心（https://clinicaltrials.gov/）检索肿瘤疫苗与肿瘤相关临床试验发现，截至2024年11月，于2024年立项及开展的临床试验立项总数已达114项，其中55项正在招募，59项未招募及状态未知（检索条件为“vaccine”and“cancer”and“Study start on or after 01/01/2024”）。 表1  2024年度肿瘤治疗性疫苗相关的临床试验 注：NCT编号为试验登记号；mRNA为信使RNA；DC为树突状细胞；GM-CSF为粒细胞-巨噬细胞集落刺激因子。 2  信使RNA（message RNA，mRNA）肿瘤疫苗 mRNA肿瘤疫苗是通过体外转录，获得编码肿瘤特异性抗原或肿瘤相关抗原的mRNA序列，制备成疫苗后注射入人体，翻译产生抗原蛋白，从而诱导机体产生特异性免疫应答[3]。与传统疫苗相比，mRNA肿瘤疫苗的优势主要在于其耐受性良好、成本较低、生产较快且能编码全长肿瘤抗原，具有良好的临床应用前景[4]。 美国BioNTech公司开发的autogene cevumeran是基于BioNTech的个体化新抗原特异性免疫疗法癌症疫苗技术平台生成的个体化新抗原疫苗。该疫苗的抗原是autogene cevumeran，其含有高达20种主要组织相容性复合体（major histocompatibility complex，MHC）Ⅰ类和MHCⅡ类分子限制的新抗原，佐剂为脂质纳米颗粒（lipid nanoparticle，LNP）。2023年6月，BioNTech在Nature上发布了autogene cevumeran个体化治疗胰腺癌Ⅱ期临床试验（NCT05968326）结果[5]。2024年AACR年会上，BioNTech公布了autogene cevumeran治疗胰腺导管腺癌的Ⅰ期临床试验（NCT04161755）的进一步进展。按照临床试验设计，受试者依次接受阿替利珠单抗、autogene cevumeran和mFOLFIRINOX化疗，此次公布的结果显示，在中位随访时间36个月时，获得新抗原特异性免疫反应患者的无复发生存（recurrence free survival，RFS）时间显著长于无疫苗激发免疫反应的患者；获得免疫反应组体内的T细胞免疫应答持续激活，中位RFS时间尚未达到（n＝8，P＝0.003），而未获得免疫反应组患者中位RFS时间为13.4个月（n＝8，P＝0.007）。 2024年3月，美国生物技术公司Gritstone bio公布了肿瘤疫苗GRANITE治疗转移性微卫星稳定型结直肠癌（microsatellite stability colorectal cancer，MSS CRC）患者Ⅱ/Ⅲ期临床试验（NCT05141721）的研究数据。GRANITE是一款个体化新抗原mRNA癌症疫苗，其新抗原是根据每例患者活检得到的肿瘤组织，进行肿瘤组织测序筛选出。GRANITE利用自扩增mRNA载体递送表达新抗原的mRNA，引发显著的CD8+细胞毒性T淋巴细胞反应，从而产生抗肿瘤效应。该疫苗目前已获得美国食品药品监督管理局（Food and Drug Administration，FDA）的快速通道资格，用于治疗MSS CRC患者。截至2024年3月8日，67例可评估疗效的转移性MSS CRC患者被随机分为GRANITE组（n＝39例，接受化疗方案FOLFOX或FOLFOXIRI＋贝伐珠单抗诱导治疗）和对照组（n＝28，接受化疗方案FOLFOX或FOLFOXIRI＋贝伐珠单抗诱导治疗）。研究结果显示，与对照组患者相比，GRANITE组的疾病进展和死亡风险降低了18%，高危患者的疾病进展和死亡风险降低了48%。GRANITE组患者的中位无进展生存时间为11.57个月，对照组仅为7.06个月。该研究结果提示，GRANITE在转移性MSS CRC患者的治疗中展现出了积极的疗效[6]。 mRNA-4157/V940是美国Moderna公司开发的一款个体化mRNA肿瘤疫苗，其抗原为包含编码最多34种新抗原的单一合成mRNA分子，佐剂为LNP[7]。其Ⅱb期临床试验（NCT03897881）3年随访数据首次在2024年ASCO年会上公布[8]。数据显示，中位随访时间约34.9个月，与单独使用帕博利珠单抗相比，mRNA-4157与帕博利珠单抗联用可使黑色素瘤患者复发和死亡风险降低49%，远处转移的风险降低了62%，且与单独使用帕博利珠单抗相比，mRNA-4157联合帕博利珠单抗的总生存（overall survival，OS）时间的探索性终点更有利，2.5年OS率分别为96.0%和90.2%，其RFS时间显著延长，RFS率提高了19.2%。Moderna公司目前启动了另一项Ⅲ期临床试验（NCT05933577），主要评估mRNA-4157联合帕博利珠单抗治疗肿瘤完全切除后、复发风险较高的ⅡB～Ⅳ期黑色素瘤患者的联合疗效。截至2024年4月，已在伦敦大学学院医院招募了首批患者[9]。 虽然截至目前尚未有临床上市的mRNA肿瘤疫苗，早期临床试验的结果也仅显示出适度的临床疗效[10]。但随着mRNA疫苗在肿瘤治疗领域展现出的广阔前景，mRNA疫苗作为未来癌症治疗关键策略的潜力巨大。数据显示，mRNA肿瘤疫苗mRNA-4157在临床试验中疗效显著且耐受性良好，预计最早可能于2025年上市，这将会是全球首款mRNA肿瘤疫苗[11]。目前国内mRNA肿瘤疫苗也已有多个产品处于临床及临床前研究阶段，如成都威斯津生物医药科技有限公司自主研发的WGc-043，可用于治疗EB病毒阳性的肿瘤，目前已通过美国FDA临床试验审批。我国自主研发的mRNA肿瘤疫苗JCXH-211也在实体瘤中开展了Ⅰ期临床试验（NCT05727839）。 3  病毒载体肿瘤疫苗 病毒载体疫苗是利用改造后具有复制缺陷或减毒的病毒作为载体，将编码肿瘤抗原的遗传信息传递给宿主细胞，促使其表达这些抗原，从而激活特异性抗肿瘤免疫反应[12]。由于病毒载体肿瘤疫苗发展相对成熟，安全性良好，传递肿瘤抗原高效，无需佐剂就能诱导强烈的特异性免疫反应，因而受到临床广泛关注[13]。 2024年4月，世界疫苗大会上公布了新型癌症疫苗VBI-1901的Ⅰ/Ⅱ期临床试验（NCT03382977）研究结果。VBI-1901是一款由美国生物制药公司VBI研发的新型癌症疫苗，其采用VBI的包膜病毒样颗粒技术进行设计，旨在通过靶向gB和pp65这2种高免疫原性的巨细胞病毒抗原，激发免疫系统的反应。该临床试验是一项多中心、随机、对照、开放标签的研究，旨在评估VBI-1901作为单药治疗复发性胶质母细胞瘤患者的疗效，包括OS率、客观缓解率以及安全性和耐受性。结果显示，接受VBI-1901治疗的5例可评估患者的疾病控制率为40%，与接受卡莫司汀或洛莫司汀标准治疗的6例可评估患者相比，平均OS时间提高了约5个月。VBI-1901在治疗复发性胶质母细胞瘤中展现出了令人鼓舞的疗效，有效控制了患者的疾病进展。目前该试验的后续研究正在持续招募患者，研究人员的目标是每组招募30人，截至2024年4月，共有14个研究中心正在积极招募患者，预期于2024年12月公布更多的中期数据[14]。 肿瘤疫苗TG4050是利用非致病型痘病毒提供的30种个性化的新抗原，激活和扩增T细胞的疫苗[15]。2024年AACR年会上公布了一项Ⅰ期临床试验（NCT04183166），目的是评估TG4050的安全性及有效性。该试验招募了口腔、口咽、下咽或喉部完全切除的Ⅲ期或Ⅳ期HPV阴性头颈鳞状细胞癌患者，将患者随机分为A组（n＝17，标准护理后立即接受TG4050治疗）和B组（n＝16，仅接受标准护理，若出现肿瘤复发，则加用TG4050治疗）。在中位随访18.6个月时，A组可评估患者（n＝16）仍处于缓解期，均未出现肿瘤复发。而B组患者中，有3例患者分别在6.2、8.8、18.5个月后出现肿瘤复发。初步试验结果表明，TG4050能激发HPV阴性头颈鳞状细胞癌患者的肿瘤特异性免疫反应，从而降低肿瘤复发率，具有抗肿瘤活性[16]。 4  新抗原树突状细胞（dendritic cell，DC）疫苗 肿瘤细胞疫苗是由来源于患者自体或同种异体的肿瘤细胞作为免疫源，经照射、加热、冷冻等处理使其失活，并辅以佐剂以提高其免疫原性，注射入患者体内激活抗肿瘤免疫反应[17]。其中DC是目前认为机体中功能最强大的专职抗原递呈细胞（antigen presenting cells，APC）[18]，其能高效摄取、加工处理和递呈抗原，从而激活T细胞介导的抗肿瘤免疫反应[19]。迄今为止，DC肿瘤疫苗已在黑色素瘤、结直肠癌、非小细胞肺癌等多种实体肿瘤的临床研究中被证实了其安全性和临床疗效[20]。 2024的AACR年会上，美国Diakonos Oncology公司公布了其DC疫苗DOC1021用于治疗多形性胶质母细胞瘤（glioblastoma，GBM）患者的Ⅰ期临床试验的中期分析结果。DOC1021疫苗是由患者自身的免疫细胞及患者肿瘤样本中提取的RNA和蛋白质结合制成，可以个性化靶向患者完整的癌症抗原谱而无需进行任何基因修饰。中期分析结果显示，接受疫苗治疗患者的中位OS时间尚未达到，但有望大幅超过接受标准治疗患者的预期中位OS时间（12.7个月）。目前可评估GBM患者的1年OS率为88%，而接受标准化治疗的GBM患者的1年OS率仅为53%[21]。 5  多肽疫苗 肿瘤多肽疫苗是基于肿瘤抗原表位氨基酸序列设计并化学合成的多肽生产的疫苗。多肽疫苗由专职APC摄取、加工、处理并进行提呈，结合T淋巴细胞抗原识别受体和共刺激分子的作用使特异性T淋巴细胞活化，从而激活强烈的抗肿瘤免疫反应[22]。多肽疫苗制备简单，生产成本低廉，化学性质稳定，具有显著优势，因而受到肿瘤生物治疗研究领域的高度重视。 Elicio Therapeutics开发的ELI-002是一种淋巴结靶向的肿瘤疫苗，包括两亲分子修饰的KRAS G12D和KRAS G12R长肽和两亲分子修饰的Toll样受体9，目前已进入Ⅰ期临床试验阶段（NCT04853017）[23]。临床前研究结果显示，注射经两亲分子修饰后的ELI-002与直接注射未经修饰的抗原肽相比，KRAS G12D免疫强度提高了400倍以上，KRAS G12R免疫强度提高了60倍以上[24]。2024年1月Nature Medicine上发表了该Ⅰ期临床试验最新研究成果，所有接受疫苗治疗的胰腺癌和结直肠癌的患者中，84%的患者出现了T淋巴细胞免疫应答，T淋巴细胞免疫反应水平高于中位数的患者中位RFS时间显著短于T淋巴细胞免疫反应水平低于中位数的患者（未达到∶4.01个月，P＜0.05），为Ⅱ期临床试验奠定了基础[25]。 2024年3月，Nature Communications上发表了一项随机多中心Ⅱ期临床试验（NCT 00118274）的长期研究结果。该研究中所有高危黑色素瘤患者均接受靶向CD8+淋巴T细胞的多肽疫苗（12MP），且随机接受了6MHP（6种黑色素瘤特异性肽抗原的混合物）或tet（破伤风类毒素肽）2种CD4+T淋巴细胞疫苗，并在研究中评估环磷酰胺（cyclophosphamide，Cy）预处理对疫苗疗效的影响。临床试验共纳入167例ⅡB～Ⅳ期黑色素瘤患者，中位年龄为55～60岁，其中82例患者接受12MP＋tet治疗，85例患者接受12MP＋6MHP治疗。所有患者的中位随访时间为8.6年，结果显示，2种疫苗方案的预计OS时间在早期相似，之后逐渐分离，事后分析表明，12MP＋6MHP的疫苗方案改善了长期OS时间。研究结果还表明，Cy预处理未产生显著效益，但多变量分析表明，Cy预处理与12MP＋6MHP的疫苗方案接种之间存在有利相互作用的可能性。表明在ⅡB～Ⅳ期黑色素瘤患者中，辅助12MP＋6MHP疫苗，可显著延长OS时间。对于部分复发可切除的患者可能会获得长期无病生存[26]。 6  总结与展望 目前，肿瘤治疗性疫苗的临床试验数量正在迅速增加，尽管取得了实质性进展，但其仍然面临着许多挑战。随着高通量基因测序和大数据分析技术的应用，新抗原疫苗备受大众关注。与传统疫苗相比，新抗原疫苗特异性强，免疫耐受性良好，可提供长期免疫保护作用，是2024年度肿瘤治疗性疫苗中的研究热点[27]。然而其开发过程中，新抗原的筛选与鉴定周期长、“冷肿瘤”免疫原性低、激活的免疫反应疗效受限是新抗原疫苗抗癌之路上存在的重重阻碍。如何开发高效、快速、个性化的新抗原预测模型和鉴定技术，通过联合疗法增强肿瘤疫苗的免疫反应则是肿瘤疫苗获得进一步突破的关键所在。肿瘤疫苗距离真正的成功转化和临床推广仍尚远，相信未来肿瘤治疗性疫苗将有进一步突破，为癌症患者带来新的希望。 参考文献 [1] THOMAS T L. 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Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial[J]. Nat Med, 2024, 30(2):531-542. [26] NINMER E K, ZHU H, CHIANESE-BULLOCK K A, et al. Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase Ⅱ trial[J]. Nat Commun, 2024, 15(1):2570. [27] GRIMMETT E, AL-SHARE B, ALKASSAB M B, et al. Cancer vaccines: past, present and future: a review article[J]. Discov Oncol, 2022, 13(1):31. 推荐阅读 ●   2023年度肿瘤学科盘点集锦(共17个) 声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。 排版：lagertha 校对：松月