Short-course neoadjuvant in situ vaccination for murine melanoma.
Short-course neoadjuvant in situ vaccination for murine melanoma.
复制标题
DOI：
10.1136/jitc-2021-003586
复制
发表时间：
2022-01
影响因子：
10.9
通讯作者：
Sondel PM
中科院分区：
文献类型：
--
作者：
Aiken TJ;Komjathy D;Rodriguez M;Stuckwisch A;Feils A;Subbotin V;Birstler J;Gillies SD;Rakhmilevich AL;Erbe AK;Sondel PM
手术切除仍然是大多数实体瘤多模式治疗的重要组成部分。新辅助免疫治疗有几个潜在的优势，包括原位肿瘤疫苗接种和手术标本反应的病理评估。我们之前描述了黑色素瘤的原位肿瘤疫苗接种策略，使用局部辐射（RT）和肿瘤内注射肿瘤特异性抗gd2免疫细胞因子（IT-IC）。在这里，我们测试了使用抗gd2免疫细胞因子的新辅助原位肿瘤疫苗接种和手术切除，而不进行RT，是否可以产生能够预防复发或远处转移的免疫记忆。携带GD2表达B78黑色素瘤的小鼠接受新辅助放疗、IT-IC或RT + IT-IC联合治疗。手术切除后进行新辅助免疫治疗。在切除标本中评估免疫浸润。对小鼠进行B78对侧侧肿瘤或肺播散实验诱导的非gd2表达B16黑色素瘤转移。用不同的治疗方案治疗的小鼠对再挑战的排斥被认为是免疫记忆的证据。新辅助IT-IC和手术切除导致CD8 T细胞浸润增加，CD8：调节性T细胞比例增加，以及对侧侧侧侧再攻击的免疫记忆。切除的时间对记忆的发展没有显著影响，记忆早在手术当天就出现了。与新辅助RT +IT -IC相比，新辅助IT-IC治疗的局部伤口毒性更小。新辅助IT-IC和切除以CD4 T细胞依赖的方式导致B16肺转移的排斥反应。新辅助的IT-IC产生了能够防止远处转移的免疫记忆，尽管对大型原发性黑色素瘤的疗效有限。通过新辅助肿瘤疫苗接种和手术相结合，避免了局部RT的毒性。这些临床前数据支持对隐匿性远处病变高风险黑色素瘤患者使用新辅助IT-IC的进一步研究。
Surgical resection remains an important component of multimodality treatment for most solid tumors. Neoadjuvant immunotherapy has several potential advantages, including in-situ tumor vaccination and pathologic assessment of response in the surgical specimen. We previously described an in-situ tumor vaccination strategy in melanoma using local radiation (RT) and an intratumoral injection of tumor-specific anti-GD2 immunocytokine (IT-IC). Here we tested whether neoadjuvant in-situ tumor vaccination using anti-GD2 immunocytokine and surgical resection, without RT, could generate immunologic memory capable of preventing recurrence or distant metastasis. Mice bearing GD2 expressing B78 melanoma tumors were treated with neoadjuvant radiation, IT-IC, or combined RT + IT-IC. Surgical resection was performed following neoadjuvant immunotherapy. Immune infiltrate was assessed in the resection specimens. Mice were rechallenged with either B78 contralateral flank tumors or pulmonary seeding of non-GD2 expressing B16 melanoma metastasis induced experimentally. Rejection of rechallenge in mice treated with the various treatment regimens was considered evidence of immunologic memory. Neoadjuvant IT-IC and surgical resection resulted in increased CD8 T cell infiltration, a higher CD8:regulatory T cell ratio, and immunologic memory against contralateral flank rechallenge. The timing of resection did not significantly impact the development of memory, which was present as early as the day of surgery. There was less local wound toxicity with neoadjuvant IT-IC compared with neoadjuvant RT +IT IC. Neoadjuvant IT-IC and resection resulted in the rejection of B16 lung metastasis in a CD4 T cell dependent manner. Neoadjuvant IT-IC generates immunologic memory capable of preventing distant metastasis despite limited efficacy against large primary melanoma tumors. By combining neoadjuvant tumor vaccination and surgery, the toxicity of local RT was avoided. These preclinical data support further investigation regarding the use of neoadjuvant IT-IC in patients with melanoma at high risk for occult distant disease.
登录
查看更多内容
DOI：
10.1126/science.aax0182
发表时间：
2020-01-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Topalian SL;Taube JM;Pardoll DM
通讯作者：
Pardoll DM
影响因子：
3.7
作者：
Ando, Nobutoshi;Kato, Hoichi;Fukuda, Haruhiko
通讯作者：
Fukuda, Haruhiko
影响因子：
158.5
作者：
Sauer, R;Becker, H;Raab, R
通讯作者：
Raab, R
影响因子：
8.8
作者：
Radny, P;Caroli, UM;Garbe, C
通讯作者：
Garbe, C
影响因子：
158.5
作者：
ROSELL, R;GOMEZCODINA, J;ABAD, A
通讯作者：
ABAD, A