Overview of interleukin-2 inhalation therapy

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Locoregional administration of interleukin-2 (IL-2) is an effective therapeutic strategy.
• Regional IL-2 delivery enhances local and systemic immunomodulation with reduced toxicity compared to systemic therapy.
• Continuous high cytokine levels in tumor tissues are achievable via regional administration.

Purpose of the Study:

• To review clinical experiences with inhaled IL-2 therapy for pulmonary metastases.
• To evaluate the efficacy and safety of inhaled IL-2 in metastatic renal cell carcinoma and other malignancies.
• To assess the benefits of locoregional IL-2 administration.

Main Methods:

• Review of clinical experiences with inhaled IL-2 therapy in approximately 300 patients.
• Detailed analysis of a 10-year single-institution experience with 188 metastatic renal cell carcinoma patients.
• Administration of recombinant IL-2 (18-36 million IU) via inhalation (90%) and subcutaneous routes (10%) until disease progression.

Main Results:

• Inhaled IL-2 prevented progression of pulmonary metastases in metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma.
• The major adverse event was dose-dependent cough; significant increases in lymphocytes and eosinophils were observed.
• In 188 metastatic renal cell carcinoma patients, pulmonary metastasis progression was prevented in 68% for a median of 7 months, significantly improving overall survival.

Conclusions:

• Inhaled IL-2 demonstrates efficacy, alone or combined with other therapies, across various malignancies.
• Low toxicity profiles offer significant quality-of-life benefits.
• Inhalation therapy provides a viable treatment option for patients unsuitable for systemic IL-2 administration.