Chronic Vaccination with a Therapeutic EGF-Based Cancer Vaccine: A Review of Patients Receiving Long Lasting Treatment

Abstract

Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials are rare. The role of therapeutic vaccines in advanced cancer patients, if any, would be to decrease the rate of disease progression and to increase survival and quality of life. Due to the redundant regulatory loops contracting the immune response to antigens that cannot be eliminated, such a role would require chronic vaccination, which is at first sight at odds with the classic experience of vaccinology. During the last decade our team has been developing a therapeutic vaccine for advanced lung cancer, which consists in human recombinant Epidermal Growth Factor (EGF) chemically conjugated to a carrier protein from Neisseria meningitides. Several clinical trials have been carried out, showing increase in anti-EGF antibody titters, decrease in plasma EGF concentration and survival advantage in vaccinated patients. In the present paper we review data from 58 patients who were vaccinated monthly for more than one or two years. Long term vaccination was feasible and safe, and there was no evidence of cumulative toxicity. Patients kept high anti-EGF antibody titters during all the time of vaccination, without evidence of immune response exhaustion. Continued vaccination increased the probability to get a high antibody response, which has been previously shown to be, in turn, associated with a better survival. Observations done in this series of patients suggest that long term therapeutic vaccination is a feasible strategy, worth to be further explored in the aim of transforming advanced cancer into a chronic disease.

Advances and Prospects in Cancer Immunotherapy

“…Vaccines, known as therapeutic cancer vaccines, are being developed to treat patients with existing cancer and are one of the most active fields in cancer research [110]. Treatment with cancer vaccines, an active immunotherapy for cancer, is a desired method for cancer patients, especially patients with cervical cancer as cervical cancer is caused by viruses, for example, human papillomavirus (HPV).…”

“…Clinical trials showed that the therapeutic telomerase-(TERT-) specific vaccine Vx-001 could induce TERT-reactive T cells and have a significant overall survival benefit in patients with chemoresistant advanced solid tumors [114]. A therapeutic vaccine, composed of epidermal growth factor (EGF) chemically conjugated to a carrier protein from Neisseria meningitides, induced anti-EGF antibody titters, decreased EGF concentration in plasma, and had survival advantages in vaccinated patients with advanced lung cancer [110]. However, there are currently no therapeutic vaccines available to treat cancers effectively.…”

Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

“…The metanalysis of 58 patients who were vaccinated monthly for more than one or two years evidenced that long term vaccination was feasible and safe, without evidences of cumulative toxicity or immune response exhaustion [65]. The results of the planned interim analysis with the first 226 patients recruited in the ongoing randomized phase III trial, vaccinating the patients who respond to first line chemotherapy with at least stable disease, in the modality of switch maintenance, beyond progression disease and until change their performance status as per physician criteria, confirm previous results in benefit the patient’s overall survival by intent to treat analysis (manuscript in preparation).…”

Intralesional Human Recombinant Epidermal Growth Factor for the Treatment of Advanced Diabetic Foot Ulcer: From Proof of Concept to Confirmation of the Efficacy and Safety of the Procedure

“…The concern is justified by the growth stimulating property of these active principles. Practically, antigrowth factor therapy is approved or extensively experimented for several neoplasia (Gonzalez et al, 2011;Caraglia et al, 2006;Geva et al, 2010). Additionally an increase in any-site cancer incidence was observed in DFU patients treated with platelet-derivedgrowth factor (PDGF; becaplermin), which generated a warning from regulatory agencies (FDA-USA, 2008).…”