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Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy.
Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy. Cancer discovery Linde, M. H., Fan, A. C., Kohnke, T., Trotman-Grant, A. C., Gurev, S. F., Phan, P., Zhao, F., Haddock, N. L., Nuno, K. A., Gars, E. J., Stafford, M., Marshall, P. L., Dove, C. G., Linde, I. L., Landberg, N., Miller, L. P., Majzner, R. G., Zhang, T. Y., Majeti, R. 2023Abstract
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.
View details for DOI 10.1158/2159-8290.CD-21-0502
View details for PubMedID 36856575