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CorrigendumOncology Free access | 10.1172/JCI26532C1

Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake

Markus Loeffler, Jörg A. Krüger, Andreas G. Niethammer, and Ralph A. Reisfeld

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Published February 2, 2009 - More info

Published in Volume 119, Issue 2 on February 2, 2009
J Clin Invest. 2009;119(2):421–421. https://doi.org/10.1172/JCI26532C1.
© 2009 The American Society for Clinical Investigation
Published February 2, 2009 - Version history
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Related article:

Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake
Markus Loeffler, … , Andreas G. Niethammer, Ralph A. Reisfeld
Markus Loeffler, … , Andreas G. Niethammer, Ralph A. Reisfeld
Research Article Oncology

Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake

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Abstract

Tumor-associated fibroblasts are key regulators of tumorigenesis. In contrast to tumor cells, which are genetically unstable and mutate frequently, the presence of genetically more stable fibroblasts in the tumor-stromal compartment makes them an optimal target for cancer immunotherapy. These cells are also the primary source of collagen type I, which contributes to decreased chemotherapeutic drug uptake in tumors and plays a significant role in regulating tumor sensitivity to a variety of chemotherapies. To specifically kill tumor-associated fibroblasts, we constructed an oral DNA vaccine targeting fibroblast activation protein (FAP), which is specifically overexpressed by fibroblasts in the tumor stroma. Through CD8+ T cell–mediated killing of tumor-associated fibroblasts, our vaccine successfully suppressed primary tumor cell growth and metastasis of multidrug-resistant murine colon and breast carcinoma. Furthermore, tumor tissue of FAP-vaccinated mice revealed markedly decreased collagen type I expression and up to 70% greater uptake of chemotherapeutic drugs. Most importantly, pFap-vaccinated mice treated with chemotherapy showed a 3-fold prolongation in lifespan and marked suppression of tumor growth, with 50% of the animals completely rejecting a tumor cell challenge. This strategy opens a new venue for the combination of immuno- and chemotherapies.

Authors

Markus Loeffler, Jörg A. Krüger, Andreas G. Niethammer, Ralph A. Reisfeld

×

Original citation: J. Clin. Invest.116:1955-1962 (2006). doi:10.1172/JCI26532.

Citation for this corrigendum: J. Clin. Invest.119:421 (2009). doi:10.1172/JCI26532C1.

In Acknowledgments, the Department of Defense grant to R.A. Reisfeld was cited incorrectly. The correct grant number is BCO50141.

The authors regret the error.

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