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Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care?

  • Focussed Research Review
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Abstract

Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh tumor tissues after ex vivo activation and extensive expansion. TIL-based ACT has so far only been tested in smaller phase I/II studies, but these studies consistently confirm an impressive clinical response rate of up to 50 % in metastatic melanoma including a significant proportion of patients with durable complete tumor eradication. These remarkable results justify the need for a definitive phase III trial documenting the efficacy of this type of T cell-based Advanced Therapy Medicinal Product in order to pave the way for regulatory approval and implementation of TIL therapy as a new treatment standard in oncology practice. TIL-based ACT can, however, only be offered to a limited group of patients based on the need for accessible tumor tissue, the complexity of TIL production procedures, and the very intensive nature of this three-step treatment including both high-dose chemotherapy and interleukin-2 in addition to T cell infusion. To this end, adoptive T cell therapy using peripheral blood mononuclear cell-derived T cells could be a welcome alternative to circumvent these limitations and broaden up the applicability of ACT. Here, we discuss current initiatives in this focused research review.

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Abbreviations

ACT:

Adoptive cell therapy

Ag:

Antigen

ATMP:

Advanced therapy medicinal products

CCIT:

Center for cancer immune therapy

IL-2:

Interleukin-2

IFN-α:

Interferon-α

IFN-γ:

Interferon-γ

MHC:

Major histocompatibility complex

MM:

Metastatic melanoma

PBMC:

Peripheral blood mononuclear cells

REP:

Rapid expansion protocol

TILs:

Tumor-infiltrating lymphocytes

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Correspondence to Inge Marie Svane.

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This paper is a Focussed Research Review based on a presentation given at the Thirteenth International Conference on Progress in Vaccination against Cancer (PIVAC 13), held in Amsterdam, the Netherlands, 2nd–4th October 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Svane, I.M., Verdegaal, E.M. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care?. Cancer Immunol Immunother 63, 1081–1091 (2014). https://doi.org/10.1007/s00262-014-1580-5

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