重编程
癌症免疫疗法
免疫疗法
癌症研究
癌症
抗原
髓系白血病
髓样
抗原提呈细胞
白血病
免疫学
免疫系统
癌细胞
接种疫苗
生物
T细胞
医学
细胞
内科学
遗传学
作者
Miles H. Linde,Amy C. Fan,Thomas Köhnke,Aaron C. Trotman-Grant,Sarah F. Gurev,Paul Phan,Feifei Zhao,Naomi L. Haddock,Kevin A. Nuno,Eric J. Gars,Melissa Stafford,Payton L. Marshall,Christopher G. Dove,Ian L. Linde,Niklas Landberg,Lindsay P. Miller,Robbie G. Majzner,Tian Yi Zhang,Ravindra Majeti
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2023-03-01
卷期号:13 (5): 1164-1185
被引量:12
标识
DOI:10.1158/2159-8290.cd-21-0502
摘要
Abstract Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAA) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid-lineage reprogramming to directly convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APC). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology. Significance: Despite recent advances, the clinical benefit provided by cancer vaccination remains limited. We present a cancer vaccination approach leveraging myeloid-lineage reprogramming of cancer cells into APCs, which subsequently activate anticancer immunity through presentation of self-derived cancer antigens. Both hematologic and solid malignancies derive significant therapeutic benefit from reprogramming-based immunotherapy. This article is highlighted in the In This Issue feature, p. 1027
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