Delving into the Latest Updates on Interferon alpha-2b/interferon gamma(Center For Genetic Engineering And Biotechnology) with Synapse

Temozolomide (TMZ) is a chemotherapeutic used for the treatment of glioblastoma. The MGMT repair enzyme (O'-(6)-methyl guanine-DNA-methyltransferase) promoter methylation is a predictive biomarker to TMZ response; interferons (IFNs) type I can downregulate MGMT expression improving survival in patients with unmethylated MGMT promoter. HeberFERON is a co-formulation of IFNs type I and II with higher antiproliferative effect over glioblastoma cell lines than individual IFNs. We investigated the proliferative response of patient-derived glioblastoma cultures to HeberFERON and its combination with TMZ in relation to MGMT promoter methylation and the regulation of MGMT transcript after HeberFERON treatment. Eleven glioblastoma-derived cultures, molecularly classified according to TCGA and MGMT promoter methylation, were assayed for proliferation inhibition with HeberFERON at low doses (1-25 IU/mL) [alone or combined with TMZ] or at higher doses (50-200 IU/mL) using CellTiter-Glo Luminescent Cell Viability Assay (Promega). Eight cultures were further treated with 100 IU/mL of HeberFERON for 72 h, total RNA purified (Qiagen) and converted to cDNA (Superscript III kit, Invitrogen) as quantitative PCR templates. Changes of MGMT&P53 transcripts level were monitored. Response of cultures to HeberFERON is variable, dose-dependent and apparently independent from TCGA classification and MGMT methylation status, based on the eight Classical cultures data. When combining HeberFERON with TMZ there was an increase in cell death for cultures, 2/4 with methylated and 5/5 with unmethylated MGMT promoter. In two out five cultures with unmethylated MGMT status, we observed a decrease of MGMT gene levels and an increase in P53 encoding gene levels. HeberFERON and TMZ combination should be further assayed in glioblastoma, mainly for those with unmethylated MGMT promoter.

01 Jan 2018·Seminars in OncologyQ3 · MEDICINE

HeberFERON, a new formulation of IFNs with improved pharmacodynamics: Perspective for cancer treatment

Q3 · MEDICINE

Review

Author: Santana-Milian, Hector ; Bello-Rivero, Iraldo ; Rios-Cabrera, Margarita ; Vazquez-Blomquistc, Dania ; Besada-Perez, Vladimir ; Garcia-Vega, Yanelda ; Duncan-Roberts, Yaquelin

The rational combination of recombinant IFN-α2b and IFN-γ resulted in a new formulation of interferons (HeberFERON) with improved pharmacodynamics. In basal cell carcinomas HeberFERON produces a more rapid antitumor effect and results in a larger number of complete responses. In patients with glioblastoma multiforme, the administration of HeberFERON after surgery and radiotherapy results in an estimated overall survival of 19 months. Patients with stage III or IV renal cell carcinoma also appear to benefit from the intravenous administration of HeberFERON, with prolongation of survival and good quality of live. HeberFERON offers a promising alternative formulation of interferons for the treatment of cancer with a very favorable safety profile.

01 Dec 2016·BMC Pharmacology and Toxicology

Pharmacokinetic and pharmacodynamic characterization of a novel formulation containing co-formulated interferons alpha-2b and gamma in healthy male volunteers

Article

Author: Pérez-Rodríguez, Sonia ; Díaz-Machado, Alina ; García-Vega, Yanelda ; Tuero-Iglesias, Ángela D ; Valenzuela-Silva, Carmen M ; Campos-Mojena, Rosario ; González-Delgado, Carlos A ; Cruz-Ramírez, Alieski ; Bello-Rivero, Iraldo ; Martín-Trujillo, Alis ; Hernández-González, Ignacio ; Santana-Milián, Héctor ; López-Saura, Pedro A ; García-García, Idrian

BACKGROUNDMore potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be achieved by combining IFN alpha and IFN gamma. The aim of this work was to characterize the pharmacokinetics and pharmacodynamics of a novel formulation containing a co-formulated combination of IFNs alpha-2b and gamma (CIGB-128-A).METHODSA group of nine healthy male subjects received intramuscularly 24.5 × 10⁶ IU of CIGB-128-A. IFN concentrations were evaluated for 48 h. Serum neopterin, beta2-microglobulin (β₂M) and 2'-5' oligoadenylate synthetase (2'-5' OAS), classical IFN-inducible serum markers, were measured during 192 h by enzyme immunoassay and body temperature was used as pharmacodynamic variable as well.RESULTSConcerning pharmacokinetics, serum IFNs' profiles were better fitted to a mono-compartmental model with consecutive zero order and first order absorption, one bioavailability value. No interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles. Neopterin and β₂M time profiles showed a delay that was efficiently linked to pharmacokinetics by means of a zero order absorption rate constant. Neopterin level was nine-fold higher than initial values, 48 h post-administration, an increment not described before. At this time, mean serum β₂M peaked around the double from baseline. Serum concentrations of the enzyme 2'-5' OAS was still elevated on the 8 day post-injection. The formulation was well tolerated. Most frequent adverse reactions were fever, headache, arthralgia and lymphopenia, mostly mild.CONCLUSIONSThe administration of co-formulated IFN alpha-2b and IFN gamma likely provides improved pharmacodynamic properties that may be beneficial to treat several malignancies.TRIAL REGISTRATIONCuban Public Registry of Clinical Trials RPCEC00000118 , May 24, 2011.

100 Deals associated with Interferon alpha-2b/interferon gamma(Center For Genetic Engineering And Biotechnology)

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Indication	Highest Phase	Country/Location	Organization	Date
Basal Cell Carcinoma	Phase 2	-	Heber Biotec SA	-
COVID-19	Discovery	CU	Centro de Ingenieria Genetica y Biotecnologia	24 Mar 2020
Brain Cancer	Discovery	CU	Centro de Ingenieria Genetica y Biotecnologia	-
Mycosis Fungoides	Discovery	CU	Centro de Ingenieria Genetica y Biotecnologia	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


RPCEC00000130 (Pubmed \| BMC Pharmacol Toxicol)	Phase 1	Mycosis Fungoides	-	HeberPAG	llcwsvvykp(pvyzjjcidn) = The most encouraging data was the high increment of serum neopterin, 8.0 ng/mL at 48 h, not been described before for any unmodified or pegylated IFN nvfbfwjptl (mxxvdahhbj ) View more	-	28 Dec 2012