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Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy

Linde, Miles H ; Fan, Amy C ; Kohnke, Thomas ; Trotman-Grant, Aaron C ; Gurev, Sarah F ; Phan, Paul ; Zhao, Feifei ; Haddock, Naomi L ; Nuno, Kevin A and Gars, Eric J , et al. (2023) In Cancer Discovery 13(5). p.1164-1185
Abstract

Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) 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-APCs). 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... (More)

Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) 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-APCs). 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.

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publishing date
type
Contribution to journal
publication status
published
in
Cancer Discovery
volume
13
issue
5
pages
1164 - 1185
publisher
American Association for Cancer Research
external identifiers
  • scopus:85158865890
  • pmid:36856575
ISSN
2159-8274
DOI
10.1158/2159-8290.CD-21-0502
language
English
LU publication?
no
id
db1bf1d2-4760-4411-88d5-f42c48f40b1e
date added to LUP
2023-03-31 16:21:35
date last changed
2024-04-19 20:35:43
@article{db1bf1d2-4760-4411-88d5-f42c48f40b1e,
  abstract     = {{<p>Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) 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-APCs). 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.</p>}},
  author       = {{Linde, Miles H and Fan, Amy C and Kohnke, Thomas and Trotman-Grant, Aaron C and Gurev, Sarah F and Phan, Paul and Zhao, Feifei and Haddock, Naomi L and Nuno, Kevin A and Gars, Eric J and Stafford, Melissa and Marshall, Payton L and Dove, Christopher G and Linde, Ian L and Landberg, Niklas and Miller, Lindsay P and Majzner, Robbie G and Zhang, Tian Yi and Majeti, Ravindra}},
  issn         = {{2159-8274}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{5}},
  pages        = {{1164--1185}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Cancer Discovery}},
  title        = {{Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy}},
  url          = {{http://dx.doi.org/10.1158/2159-8290.CD-21-0502}},
  doi          = {{10.1158/2159-8290.CD-21-0502}},
  volume       = {{13}},
  year         = {{2023}},
}