Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy

Abstract

Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-α2a and IFN-α2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-α2a and IFN-α2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for immunostimulation in cancer patients.

Colorectal Cancer Immunotherapy: Options and Strategies

“…Cytokines are one of the potential polypeptides used in immunotherapy since they can enhance patients' immune responses well. Three recombinant cytokines such as recombinant interferon-alpha and interleukin-2 drugs have been approved by the FDA and EMA for the treatment of several malignancies ( Table 7) (208). A renewed interest in the anti-tumor properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents but also in combination with other immunomodulatory drugs.…”

Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

“…An increasing number of infection sensors and immune regulators are being explored for cancer therapy. This is reflected in the continuously growing global immune-oncology drug pipeline, which is currently led by immune checkpoint targeting biologics like PD-1 antagonists [127,167].…”

Possibilities of using NK cells in cancer immunotherapy

“…Ponadto chimeryczna postać zmodyfikowanej IL-2, poddana fuzji z przeciwciałami swoistymi dla antygenu karcinoembrionalnego (CEA -carcino--embryonic antigen) lub z białkiem aktywującym fibroblasty (FAP -fibroblast activation protein) weszła w I fazę badań klinicznych. Obecnie w licznych badaniach klinicznych testowane są: niska dawka IL-2 zarówno w formie monoterapii, jak i w połączeniu z w formie monoterapia lub w połączeniu z adoptywnym transferem komórek NK i T jako szczepionki [52].…”

“…2013[48], oraz García-Martínez i wsp. 2018[52].badaniach doszło do wytworzenia reakcji immunologicznej, niemniej jednak znacznie bardziej pożądane efekty uzyskano podczas podawania egzogennych komórek NK aktywowanych IL-2 niż w sytuacji systematycznego podawania IL-2 bezpośrednio do ustroju. W ostatniej dekadzie, na skutek lepszego zrozumienia biologii i rozwoju komórek NK, opracowano efektywne procedury izolacji i ekspansji komórek NK, które pozwoliły na otrzymanie zmodyfikowanych komórek o satysfakcjonującej jakości klinicznej.…”