Interferon alfa-2a, recombinant

To report on topical treatment with interferon (IFN) alfa-2a for conjunctival primary acquired melanosis (PAM) with atypia.

A retrospective interventional case series.

Patients diagnosed with PAM with atypia.

Patients received topical IFN α-2a, IFN α-2b, or pegylated IFN α-2a. Treatment duration, response, adverse effects, and progression-free survival (PFS) were assessed. Data was collected from the medical records of the patients with institutional review board approval.

Response to treatment and PFS.

Treatment duration ranged from 1 to 10 months, with an average follow-up of 10.48 years. A complete clinical response was observed in 11 of 12 patients (93%) after an average of 5.1 months of treatment. The average PFS was 52.5 months (4.3 years), with only one patient experiencing recurrence after 13 months. Treatment was well tolerated; five patients reported mild adverse effects, including dry eye, redness, and blurred vision. Two patients experienced more severe side effects, leading to treatment discontinuation. No limbal stem cell damage was observed in patients treated with IFN alone.

Topical IFN α-2a is safe and effective for treating PAM with atypia and for PAM with atypia surrounding conjunctival melanoma that arises from PAM with atypia, with high response rates and little to no toxicity. Its similarity to IFN α-2b and safety profile make IFN α-2a a good alternative. Further large-scale, controlled studies are needed to validate these findings and their role in clinical practice.

Interferon-α2a (IFN-α2a), a cell-signaling therapeutic protein, is effective in treating diseases such as cancer and hepatitis. However, their clinical application is limited by rapid degradation and clearance from the body. PEGylation improves its stability and in vivo circulation time but raises concerns over immunogenicity and poor biodegradability. Polysarcosine (PSar), a biodegradable and biocompatible polypeptoid with PEG-like solubility, reduced immune recognition, and tunable properties, presents a promising alternative to PEG. We present here all-atom molecular dynamics (MD) simulations demonstrating that the interactions and stabilizing effects of polysarcosine (PSar) are similar to those of poly(ethylene glycol) (PEG) on IFN-α2a. Both polymers preserve the native protein fold across concentrations, with PSar producing a lower root-mean-square deviation (RMSD) of protein residues from their reference configurations than does PEG. Both polymers suppress hydrogen bonding of the protein with water by up to 10% at polymer concentrations typically produced by PEGylation, while creating similarly large numbers of polymer contacts with IFN-α2a, mostly, but not exclusively, with polar residues, suggesting that PSar is likely just as effective as PEG in preventing IFN-α2a aggregation. These atomistic insights highlight the enhanced ability of PSar to retain the structural stability of IFN-α2a, shielding it against aggregation as well as does PEG, reinforcing its potential as a next-generation, nonimmunogenic alternative to PEG for therapeutic protein stabilization.