Table 2 Approaches and strategies for optimizing IL-2/IL-2R targeted therapies in the context of tumor microenvironment complexity
From: Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies
Approach | Description | Examples | References |
|---|---|---|---|
Interleukin-2/Interleukin-2 Receptor Axis | The use of IL-2 or agents that target the IL-2 receptor to enhance antitumor immune responses by activating T cells. | High-dose IL-2 therapy, low-dose IL-2 therapy, Treg-depleting antibodies, anti-IL-2 receptor antibodies. | (68, 69, 70, 71) |
Combination Therapies | Combination therapies that target multiple components of the tumor micro-environment can enhance treatment efficacy. | Combination of IL-2 with immune checkpoint inhibitors, chemotherapy, radiation therapy, or other immunomodulatory agents. | (10, 72, 73) |
Interleukin-2/Interleukin-2 Receptor-Targeted Antibodies | Antibodies that target the IL-2 or IL-2 receptor can enhance antitumor immune responses by blocking inhibitory signals. | Anti-IL-2 antibodies, anti-IL-2 receptor antibodies, anti-CD25 antibodies. | (68, 69, 71, 74, 75) |
Small Molecule Inhibitors | Small molecule inhibitors can block signaling pathways that inhibit T cell activation and proliferation in the tumor micro-environment. | JAK inhibitors, MEK inhibitors, PI3K inhibitors. | (76, 77, 78, 79) |
Adaptive Dosing | This approach involves adjusting the dose of IL-2 or other immunomodulatory agents based on patient response, with the goal of maximizing treatment efficacy while minimizing toxicity. | Dose escalation or de-escalation of IL-2 based on clinical response, or personalized dosing based on pharmacokinetic and pharmacodynamic parameters. | (80, 81, 82) |
Localized Delivery | Localized delivery of IL-2 or other immunomodulatory agents to the tumor micro-environment can enhance treatment efficacy while reducing systemic toxicity. | Localized delivery using drug-eluting implants, nanoparticles, or viral vectors. | (83, 84, 85, 86, 87) |
Gene Therapy | Gene therapy involves modifying immune cells or tumor cells to enhance antitumor immune responses. For example, IL-2 gene therapy can be used to deliver IL-2 directly to tumor cells, which may enhance T cell activation and proliferation in the tumor micro-environment. | CAR T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, or gene therapy using viral vectors to deliver IL-2 or other immunomodulatory agents. | (88, 89, 90, 91, 92) |
Combination with Conventional Therapies | IL-2-based therapies can be combined with conventional cancer treatments, such as chemotherapy or radiation therapy, to enhance treatment efficacy. | Combination of IL-2 with cisplatin or vinblastine, or the combination of IL-2 with radiation therapy. | (68, 74, 93, 94, 95, 96) |