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The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies. Its incidence continues to rise worldwide with a rate of 2% per year. Approximately, one-third of the RCC patients are diagnosed at advanced stages due to the asymptomatic nature of its early stages. This represents a great hurdle, since RCC is largely chemoresistant/radioresistant, and targeted therapy of mRCC still has limited efficacy. The 5-year survival rate of metastatic RCC (mRCC) is only around 10%. Adoptive cell transfer (ACT), a particular form of cell-based anticancer immunotherapy, is a promising approach in the treatment of mRCC. The vaccination principle, however, faces unique challenges that preclude the efficacy of ACT. In this article, we review the main challenges of ACT in the treatment of mRCC and describe multiple methods that can be used to overcome these challenges. In this respect, the ultimate purpose of this review is to provide a descriptive tool by which to improve the development of novel protocols for ACT of mRCC.

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Abbreviations

ACT:

Adoptive cell transfer

ccRCC:

Clear cell RCC

IL:

Interleukin

ITF:

Intratumoral fibrosis

mRCC:

Metastatic RCC

NK cell:

Natural killer cell

non-ccRCC:

Non-clear cell RCC

PBMC:

Peripheral blood mononuclear cell

PECAM:

Platelet endothelial cell adhesion molecule

RCC:

Renal cell carcinoma

TIL:

Tumor-infiltrating lymphocyte

TRAIL:

TNF-related apoptosis-inducing ligand

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Acknowledgement

We would like to thank Prof. Ilja Striz and Dr. Alasdair M. Gilfillan for a critical review of the manuscript.

Funding

Charles University—project GA UK No. 364218 and PRIMUS/MED/12 and funding by the Ministry of Health, Czech Republic—project AZV 16-28135A.

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Authors and Affiliations

  1. Institute of Immunology, 2nd Faculty of Medicine and Motol University Hospital, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic

    Zuzana Strizova, Jirina Bartunkova & Daniel Smrz

Authors
  1. Zuzana Strizova
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  2. Jirina Bartunkova
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  3. Daniel Smrz
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Contributions

Zuzana Strizova drafted and wrote the manuscript. Jirina Bartunkova contributed to the intellectual content and writing of the manuscript. Daniel Smrz contributed to the intellectual content and with Zuzana Strizova wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Daniel Smrz.

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Conflict of interest

The authors Zuzana Strizova and Daniel Smrz declare that there is no conflict of interest regarding this article. Jirina Bartunkova is a part-time employee and a minority shareholder of SOTIO, a.s., a biotech company developing cell-based immunotherapy.

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Strizova, Z., Bartunkova, J. & Smrz, D. The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma. Cancer Immunol Immunother 68, 1831–1838 (2019). https://doi.org/10.1007/s00262-019-02359-z

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