Abstract
Purpose: This work is aimed to show briefly, the clinical development of a new pharmaceutical formulation of interferons for the treatment of basal cell carcinoma. Methods: A rationale design of the combination of IFN-a2b and -γ based in their anti-proliferative synergism on several tumors cell lines identified adequate proportions to be combined to obtain the best clinical results. The potential mechanism of antitumoral effect was studied by qPCR mRNA quantification. HEBERPAG (anti-proliferative synergistic combination of co-formulated recombinant interferons-a2b and –γ) was used in clinical trials in adult patients with non-melanoma skin cancer. Trials were conducted after approval by the ethics review boards of the institutions participating in trials; and the patients gave their written informed consent to be enrolled in the studies and receive HEBERPAG. Results: HEBERPAG inhibits the proliferation of several tumor cell lines in vitro and in vivo. The combination has improved pharmacodinamic properties. Several clinical trials have demonstrated the efficacy of HEBERPAG in BCC, with excellent cosmetic effect and well tolerable, mild side effects. HEBERPAG was approved by State Control Center for Drug, Medical Equipment and Devises in Cuba, for the treatment of basal cell carcinoma of any subtype, size and localization, and adjuvant to other treatments, surgical or not. After 3-year follow-up, a recurrence rate of 0.03% was detected in treated patients. Conclusions: HEBERPAG is a novel formulation of IFNs, more potent than separated IFNs for the treatment of basal cell carcinoma, with more rapid and prolonged clinical effect and excellent cosmetic effect and safety profile.
Highlights
Basal cell carcinoma (BCC) is the most common form of skin cancer, largely caused by exposure to ultraviolet radiations [1], presumably partly because of resulting immune suppression [2]
During the in vitro and in vivo preclinical studies, were identified the best combinations that lead to growth inhibition of several tumor cells lines, including basal cell carcinoma primary cultures from biopsies of patients with BCC as well as established cells lines (Hep-2, Cervical carcinoma, ATCC:CCL23), HepG2, Hepatoma, ATCC: HB8065, and NCI-H125, Non-small cell lung cancer)
HEBERPAG inhibits the proliferation of several tumor cell lines in vitro, representative of BCC, cervical carcinoma (Hep-2), non-small cell lung carcinoma (H-125), and malignant glioma (U87MG)
Summary
Basal cell carcinoma (BCC) is the most common form of skin cancer, largely caused by exposure to ultraviolet radiations [1], presumably partly because of resulting immune suppression [2]. P53 mutations have been shown in 30% to 50% of BCCs studied, and more than half of these mutations were UV-specific. BCC has been shown to evade T cell response by secreting IL-10, by shedding ICAM-1 or by down-regulation of IFN-γ receptors and some of its mediated activities and by killing infiltrating cytotoxic T cells [5, 6]. Recurrence of BCC is not uncommon, approximately 12% with most treatment modalities. Aggressive histological BCC types are more prone to incomplete excision, recurrence, and metastasis. As cryosurgery, curettage, radiotherapy (RT), photodynamic therapy (PDT), do not allow histological confirmation of tumor clearance [8]
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