Combination immunotherapy with interleukin-2 surface-modified tumor cell vaccine and programmed death receptor-1 blockade against renal cell carcinoma.
IL2 is a type I cytokine that is associated, when given at high doses intravenously, with durable regressionin a subset of patients with metastatic melanoma and renal cell carcinoma, yet high toxicity limits its use.
While IL-2 targets anti-tumor cytotoxic lymphocytes (CTLs) for the treatment of patients with melanoma or renal cell carcinoma, IL-2 directed at regulatory T (Treg) cells could have potential therapeutic value in several immune-related diseases including chronic graft-versus-host disease (cGVHD), type 1 diabetes (T1D) and systemic lupus erythematosus (SLE).
Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin-2 and interferon-alfa, the clinical outcomes of these therapies are unsatisfactory.
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies.
The combination of L19-IL2 and the new small-molecule-drug conjugate also eradicated cancer in 100% of immunocompetent mice, bearing subcutaneously grafted CT26 colorectal cancer cells, which stably expressed carbonic anhydrase IX.<b>Conclusions:</b> These findings may be of clinical significance, because carbonic anhydrase IX is overexpressed in the majority of clear cell renal cell carcinomas and in approximately 30% of colorectal cancers.
Historically, complete tumor regression in metastatic RCC is achievable in a minority of patients through traditional immunotherapies such as high-dose interleukin-2 (IL-2) (Fyfe et al. in J Clin Oncol 13(3):688, 1995) and interferon-alfa (IFNa) (Negrier et al. in N Engl J Med 338(18):1272, 1998); however due to the significant rate of toxicities and low efficacy; accordingly the targeted therapy with tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor-antibodies (VEGF) became the standard and prevalent treatment approach for advanced RCC both in front and subsequent lines of therapy (Escudier et al. in Ann Oncol.25(Suppl 3):iii49-iii56, 2014).
Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin<sup>R</sup> Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIM<sup>SM</sup>) beginning in 2011.
Bonferroni-adjusted multivariate logistic regression was conducted to investigate the independent associations between imaging features and response after controlling for demographics, doses of IL-2, and RCC prognostic scales (eg, Heng and the Memorial Sloan Kettering Cancer Center [MSKCC]).
Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)-2) induce durable responses in a fraction of mRCC patients, and multikinase inhibitors (e.g., sunitinib or sorafenib) or anti-VEGF receptor monoclonal antibodies (mAb) are largely palliative, as complete remissions are rare.
A retrospective chart review of 40 health records of patients with melanoma or renal cell carcinoma who were treated with HD IL-2 was conducted to determine compliance to the SOS.
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s.
Although high-dose interleukin 2 immunotherapy has been superseded as first-line therapy for RCC by promiscuous receptor tyrosine kinase inhibitors (rTKIs) such as sunitinib, sunitinib itself is a potent immunoadjunct in animal tumor models.
To analyse and then generalize the mechanism by which partial or complete response is achieved among a limited number of patients with metastatic renal cell carcinoma (RCC) treated with interferon or interleukin-2.