The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers.
The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers.
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DOI：
10.1007/s10549-022-06562-y
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发表时间：
2022-07
影响因子：
3.8
通讯作者：
Overmoyer, Beth
中科院分区：
文献类型：
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作者：
Anderson, Karen S.;Erick, Timothy K.;Chen, Meixuan;Daley, Heather;Campbell, Margaret;Colson, Yolonda;Mihm, Martin;Zakka, Labib R.;Hopper, Marika;Barry, William;Winer, Eric P.;Dranoff, Glenn;Overmoyer, Beth
免疫的抗原靶点和疫苗在乳腺癌中的作用尚不清楚。我们在转移性乳腺癌和II-III期乳腺癌患者中进行了一项自体GM-CSF分泌乳腺癌疫苗的I期研究。将编码GM- = 的复制缺陷型腺病毒载体导入转移性(n = 15)和II-III期(N CSF7)患者的肿瘤细胞，然后进行照射。分别有12名和7名转移性和II-III期患者每周接种疫苗，为期三周，然后每隔一周接种一次，直到疾病进展或疫苗供应耗尽(转移性)或直到接种了6剂疫苗(II-III期)。在接种疫苗的转移性疾病患者中，8人在2个月后病情恶化，3人病情稳定4-13个月，1人13年内没有疾病证据。在II-III期疾病的患者中，5人在开始接种疫苗后1.16至8.49年间死于转移疾病(中位数6.24年)，2人截至2021年9月存活。毒副作用包括注射部位反应、疲劳、发热、上呼吸道症状、关节疼痛、恶心和浮肿。在5名可评估的转移性疾病患者中，有4人在第五次注射未经修饰的照射肿瘤细胞后出现皮肤反应，并伴有免疫细胞渗透。我们的结论是，可以从转移性或II-III期乳腺癌患者身上获取肿瘤细胞，以制备毒性有限、诱导协调免疫反应的自体GM-CSF分泌疫苗。ClinicalTrials.gov，NCT00317603(2006年4月25日)和NCT00880464(2009年4月13日)。网上版载有补充材料，可在10.1007/s10549-022-06562-y查阅。
The antigenic targets of immunity and the role of vaccination in breast cancer are unknown. We performed a phase I study of an autologous GM-CSF-secreting breast cancer vaccine in patients with metastatic and stage II–III breast cancer. Tumor cells from patients with metastatic (n = 15) and stage II–III (n = 7) disease were transduced with a replication-defective adenoviral vector encoding GM-CSF, and then irradiated. Twelve and seven patients with metastatic and stage II–III disease, respectively, received weekly vaccination for three weeks, followed by every other week until disease progression or vaccine supply was exhausted (metastatic) or until six total vaccine doses were administered (stage II–III). Among those patients with metastatic disease who received vaccinations, eight had progressive disease at two months, three had stable disease for 4–13 months, and one has had no evidence of disease for 13 years. Of the patients with stage II–III disease, five died of metastatic disease between 1.16 and 8.49 years after the start of vaccinations (median 6.24 years) and two are alive as of September 2021. Toxicities included injection site reactions, fatigue, fever, upper respiratory symptoms, joint pain, nausea, and edema. Four of five evaluable patients with metastatic disease developed a skin reaction with immune cell infiltration after the fifth injection of unmodified, irradiated tumor cells. We conclude that tumor cells can be harvested from patients with metastatic or stage II–III breast cancer to prepare autologous GM-CSF-secreting vaccines that induce coordinated immune responses with limited toxicity. clinicaltrials.gov, NCT00317603 (April 25, 2006) and NCT00880464 (April 13, 2009). The online version contains supplementary material available at 10.1007/s10549-022-06562-y.
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影响因子：
20.3
作者：
Maecker, B;Sherr, DH;Schultze, JL
通讯作者：
Schultze, JL
生物标志物和早期发现卵巢癌的策略。
DOI：
10.1158/1055-9965.epi-20-1057
发表时间：
2020-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Bast RC Jr;Lu Z;Han CY;Lu KH;Anderson KS;Drescher CW;Skates SJ
通讯作者：
Skates SJ
影响因子：
15.9
作者：
Knutson, KL;Schiffman, K;Disis, ML
通讯作者：
Disis, ML
影响因子：
5.4
作者：
Held, G;Matsuo, M;Renner, C
通讯作者：
Renner, C
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF