Although clinically effective, the actions of IFNα, either produced endogenously or by therapeutic delivery, remain poorly understood. Emblematic of this research gap is the disparate array of notable side effects that occur in susceptible individuals, such as neuropsychiatric consequences, autoimmune phenomena, and infectious complications. We hypothesised that these complications are driven at least in part by dysregulated cellular metabolism. Male Wistar rats were treated with either 170,000 IU/kg human recombinant IFNα-2a or BSA/saline (0.9% NaCl) three times per week for three weeks. Bone marrow (BM) immune cells were isolated from the excised femurs for glycolytic rate and mitochondrial function assessment using Agilent Seahorse Technology. Frequencies of immune cell populations were assessed by flow cytometry to determine whether leukopoietic changes had occurred in both blood and BM. Plasma levels of lactate and succinate were also determined. BMDMs were metabolically assessed as above, as well as their metabolic response to an antigenic stimulus (iH37Rv). We observed that BM immune cells from IFN-treated rats exhibit a hypermetabolic state (increased basal OCR/GlycoPER) with decreased mitochondrial metabolic respiration and increased non-mitochondrial OCR. Flow cytometry results indicated an increase in immature granulocytes (RP1- SSChi CD45lo) only in the blood, together with increased succinate levels in the plasma. BMDMs from IFN-treated rats retained the hypermetabolic phenotype after differentiation and failed to induce a step-up in glycolysis and mitochondrial respiration after bacterial stimulation. This work provides the first evidence of the effects of IFNα treatment in inducing hypermetabolic immune features that are associated with markers of inflammation, leukopoiesis, and defective responses to bacterial stimulation.

01 Apr 2022·Journal of the European Academy of Dermatology and Venereology

The use of pegylated interferon a‐2a in a cohort of Greek patients with mycosis fungoides

Letter

Author: Tsamaldoupis, A. ; Koumourtzis, M. ; Georgiou, E. ; Lampadaki, K. ; Stratigos, A. ; Kyriakou, A. ; Avgeros, C. ; Nikolaou, V. ; Papadavid, E. ; Koletsa, T. ; Lazaridou, E. ; Patsatsi, A.

IFN-α with its cytotoxic effects on tumorous T cells was introduced in the treatment of cutaneous T-cell lymphoma in the 1980s and is included as an option in CTCL guidelines.However, recombinant IFN α-2a or IFN α-2b interferon regimens are no longer available, and therefore, the pegylated analog (pegylated IFN α-2a) has been currently used.Nevertheless, treatment outcomes have only been reported in case reports and in a few clin. trials.The current study aimed to evaluate the efficacy and safety profile of peg IFN in the treatment of mycosis fungoides (MF).

01 Jan 2019·British Journal of CancerQ1 · MEDICINE

Cytokines in clinical cancer immunotherapy

Q1 · MEDICINE

Review

Author: Etxeberria, Iñaki ; Ponz-Sarvise, Mariano ; Castañón, Eduardo ; Aznar, Maria A ; Melero, Ignacio ; Sanmamed, Miguel F ; Pérez-Gracia, José Luis ; Rodríguez-Ruiz, María E ; Ochoa, María C ; Berraondo, Pedro

Cytokines are soluble proteins that mediate cell-to-cell communication. Based on the discovery of the potent anti-tumour activities of several pro-inflammatory cytokines in animal models, clinical research led to the approval of recombinant interferon-alpha and interleukin-2 for the treatment of several malignancies, even if efficacy was only modest. These early milestones in immunotherapy have been followed by the recent addition to clinical practice of antibodies that inhibit immune checkpoints, as well as chimeric antigen receptor T cells. A renewed interest in the anti-tumour properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents, but also in combination with other immunomodulatory drugs. These second-generation drugs under clinical development include known molecules with novel mechanisms of action, new targets, and fusion proteins that increase half-life and target cytokine activity to the tumour microenvironment or to the desired effector immune cells. In addition, the detrimental activity of immunosuppressive cytokines can be blocked by antagonistic antibodies, small molecules, cytokine traps or siRNAs. In this review, we provide an overview of the novel trends in the cytokine immunotherapy field that are yielding therapeutic agents for clinical trials.

100 Deals associated with Recombinant interferon alpha-2a(Shanghai Tenry Pharmaceutical Co. Ltd.)

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Indication	Country/Location	Organization	Date
Neoplasms	CN	Shanghai Tenry Pharmaceutical Co. Ltd.	01 Jan 2000
Virus Diseases	CN	Shanghai Tenry Pharmaceutical Co. Ltd.	01 Jan 2000

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


FNCLCC - FFCD 9710 (ASCO2006)	Phase 3	Carcinoid Tumor	63	Interferon alpha 2a recombinant	(jajweqazvn) = alrtgdpaxf uwlbujgsyu (imwjxkqycz )	Negative	20 Jun 2006
				5FU plus streptozotocin5FU plus streptozotocin	(jajweqazvn) = uoqyeyqwmc uwlbujgsyu (imwjxkqycz )

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