Renials
Reniale is the trade name for a biological drug that is used as a cancer immunotherapeutic agent for aftercare in patients with kidney cancer . Reniale is used after the kidney tumor has been surgically removed ( nephrectomy ) in adult patients whose tumor has not (yet) metastasized, meaning that it has not yet been detectably spread to other parts of the body outside the kidney. The aim of treatment with Reniale is to prevent the recurrence of tumors or metastases after the kidney has been completely or partially removed.
Clinical information
Initial clinical investigations showed a significant improvement in overall survival and progression-free survival after an observation period of 5 years. These initial results were verified in a phase III clinical trial involving 558 patients. Here, the percent tumor-free survival ( progression-free survival ) of the patients treated with Reniale after 70 months of observation was 72%, compared with 59.3% for untreated patients. A second independent evaluation of the study populations with data on the extension of overall survival ( survival rate ) over a period of up to 105 months confirmed the clinical data.
A further 990 patient meta-analysis assessing overall survival over an observation period of 10 years showed an overall survival percentage of 53.6% for patients with a stage T3 tumor compared with 36.2% for patients who were not treated with Reniale.
Pharmacological properties
The mechanism of action is based on a type IV hypersensitivity reaction and the associated activation or restoration of an immune response that already exists but is suppressed in the tumor environment , which specifically eliminates tumor cells remaining in the patient.
Preclinical studies have shown that the mechanism of action essentially takes place with the participation of immunocompetent, CD8-positive cells (e.g. cytotoxic T cells ).
After intradermal injection, the product interacts with antigen-presenting cells of the skin (e.g. macrophages ). It is generally known that, among other things, they process antigens in vivo and present them bound to MHC . This activates CD8-positive cells, which in turn recognize and kill tumor cells that have remained in vivo.
Other Information
In the course of its development, the tumor undergoes various changes (mutations), which leads to a heterogeneous nature of the tumor with regard to its surface antigens. This property has been extensively proven experimentally. For this reason, an individual drug is produced for each patient ( autologous therapy ), whereby the highly individual tumor tissue is used as a starting material and processed into cell fragments, in order to then administer the drug obtained from it to the patient in the upper arm, bypassing the tumor escape mechanisms .
Individual evidence
- ↑ Repmann R et al .: Adjuvant therapy of renal cell carcinoma patients with an autologous tumor cell lysate vaccine: a 5-year follow-up analysis. Anticancer Res. 2003; Mar-Apr; 23 (2A): 969-74 PMID 12820332
- ↑ Jocham D et al .: Adjuvant autologous renal tumor cell vaccine and risk of tumor progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomized controlled trial. Lancet. 2004 Feb 21; 363 (9409): 594-9 PMID 14987883
- ↑ Doehn C et al .: Prolongation of progression-free and overall survival following an adjuvant vaccination with Reniale in patients with non-metastatic renal cell carcinoma: secondary analysis of a multicenter phase-3 trial. Abstract presented at the German Cancer Congress, 22–26 March 2006, Berlin, Germany
- ↑ May M et al .: Ten-year survival analysis for renal carcinoma patients treated with an autologous tumor lysate vaccine in an adjuvant setting. Cancer Immunol Immunother. 2010 May; 59 (5): 687-95 PMID 19876628
- ↑ Doehn C et al .: Mode-of-Action, Efficacy, and Safety of a Homologous Multi-Epitope Vaccine in a Murine Model for Adjuvant Treatment of Renal Cell Carcinoma. Eur Urol. 2009 Jul; 56 (1): 123-31 PMID 18550267
- ↑ Hume DA. Macrophages as APC and the dendritic cell myth. J Immunol 2008; 181: 5829-5835 PMID 18941170
- ^ Wittke S et al .: Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine. OncoTargets and Therapy 2016, 9: 523-537 PMID 26889089