Abstract
For many cancer types, the immune system plays an essential role in their development and growth. Based on these rather novel insights, immunotherapeutic strategies have been developed. In the past decade, immune checkpoint blockade has demonstrated a major breakthrough in cancer treatment and has currently been approved for the treatment of multiple tumor types. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) or gene-modified T cells expressing novel T cell receptors (TCR) or chimeric antigen receptors (CAR) is another strategy to modify the immune system to recognize tumor cells and thus carry out an anti-tumor effector function. These treatments have shown promising results in various tumor types, and multiple clinical trials are being conducted worldwide to further optimize this treatment modality. Most successful results were obtained in hematological malignancies with the use of CD19-directed CAR T cell therapy and already led to the commercial approval by the FDA. This review provides an overview of the developments in ACT, the associated toxicity, and the future potential of ACT in cancer treatment.
Highlights
In the past few decades, the potency of the immune system in the development and treatment of cancer has been a major focal point of research [1]
Adoptive cell therapy (ACT) can be classified into three different types with each their own mechanism of action, namely ACT with tumor-infiltrating lymphocytes (TIL), ACT using T cell receptor (TCR) gene therapy, and ACT with chimeric antigen receptor (CAR) modified T cells [4]
Combining T cell growth factor IL-2 with the TIL infusion product resulted in a greater therapeutic potency of TIL compared to lymphokine-activated killer (LAK) cells produced from peripheral blood lymphocytes in the presence of IL-2 in mice with metastases from various tumor types
Summary
In the past few decades, the potency of the immune system in the development and treatment of cancer has been a major focal point of research [1]. Adoptive cell therapy (ACT) may provide an additional treatment option for these patients and comprises the intravenous transfer of either tumor-resident or peripheral blood modified immune cells into cancer patients to mediate an anti-tumor function. The current TIL therapy consists of ex vivo expansion of TIL from resected tumor material and adoptive transfer into the patient following a lymphodepleting preparative regimen and subsequent support of interleukin-2 (IL-2) With this regimen, remarkable objective tumor responses of around 50% have been achieved in patients with metastatic melanoma in several phase I/II clinical trials [7–9]. To the naturally occurring TILs in tumors and the thereupon-based treatment options, peripheral blood T cells can be isolated and genetically modified in vitro to express TCRs that target specific tumor antigens for the use of ACT. Rosenberg (SB, NIH, Bethesda, Maryland, US) was the first to demonstrate the anti-tumor activity of TIL in vivo in murine models in the 1980s of the
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