Drinkable gene therapy foam for the treatment of constrictive esophageal carcinoma

Patients diagnosed with esophageal cancer (EC) currently rely on treatments given at specialist care centers (surgery, chemotherapy, radiation), which despite their low cure rates are extremely life-disruptive, cause severe pain, and have strong side effects. In particular, dysphagia is one of the most distressing and debilitating symptoms in patients with cancer-related esophageal obstruction. There is clearly an urgent need for new effective and accessible therapies for EC patients that allow patients to continue normal activity as much as possible. Here, we describe a drinkable methylcellulose/xanthan gum-based gene therapy foam that coats the esophagus and accumulates an apoptosis-inducing gene therapy drug (mRNA lipid nanoparticles encoding Pseudomonas exotoxin A) at the tumorous esophageal stricture. In an in vitro EC tissue model, we show that gene therapy foam induces 110-fold higher tumor regression compared to suspension treatment. We also establish that gene therapy foam given prior to radiotherapy strongly enhances anti-tumor effects. Once implemented in the clinic, this treatment, which can be administered orally by a local family doctor or at home by the patient or caregiver, could maximize the time EC patients can live normal lives outside of the hospital and allow them to maintain their ability to swallow and eat.