Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy
(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.
(Less)
- author
- publishing date
- 2023-03-01
- 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}}, }