[1][2][3] As a special feature, terminally differentiated CD3+CD56+ CIK cells possess the capacity for both MHC-restricted and MHC-unrestricted anti-tumor cytotoxicity.
These properties, inter alia, rendered CIK cells attractive as a potential therapy for cancer and viral infections.
[5] It has been shown that lymphocytes, when exposed to interferon-gamma, anti-CD3 antibody, interleukin-1 and interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic.
Furthermore, it has been shown that CIK cells have a relevant expression of FcγRIIIa (CD16a), which can be exploited in combination with clinical-grade mAbs to redirect their activity in an antigen-specific manner.
[7][8] Recently, it has been demonstrated the efficacy of a combined approach (CIK + Cetuximab) against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options.
The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset.
Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells.
This unique combination of T-cell and NK-cell capabilities exerts a potent and widely MHC-unrestricted anti-tumor cytotoxicity against a broad range of cancer cells.
These receptors and surface markers confer the capability of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors.
Particularly solid and hematologic tumor cells tend to overexpress NKG2D ligands, making them a sought target of CIK cell-mediated cytolysis.
In many cases, CIK cell treatment led to complete remissions of tumor burden, prolonged survival durations and improved quality of life, even in advanced disease stages.