Reprogramming Cancer into Antigen-Presenting Cells as a Novel Immunotherapy.

Autor:	Linde MH; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Fan AC; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Köhnke T; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Trotman-Grant AC; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Gurev SF; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Phan P; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Zhao F; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Haddock NL; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California., Nuno KA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Gars EJ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California.; Department of Pathology, Stanford University, Stanford, California., Stafford M; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Marshall PL; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California., Dove CG; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Linde IL; Immunology Graduate Program, Stanford University School of Medicine, Stanford, California.; Department of Pathology, Stanford University, Stanford, California., Landberg N; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Miller LP; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Majzner RG; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Pediatrics, Stanford University School of Medicine, Stanford, California., Zhang TY; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California., Majeti R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.; Cancer Institute, Stanford University School of Medicine, Stanford, California.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2023 May 04; Vol. 13 (5), pp. 1164-1185.
DOI:	10.1158/2159-8290.CD-21-0502
Abstrakt:	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. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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