A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: Report of a pilot clinical trial

Abstract

We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.

HER1-ECD vaccination dispenses with emulsification to elicit HER1-specific anti-proliferative effects

“…5 Several reports show the undesirable effect of this oily adjuvant when using in human vaccination. 8,17,18 Considering the potent adjuvant effect demonstrated for VSSP 9,19 and with the aim of introducing this vaccine into a clinical setting, we evaluated a new formulation of HER1-ECD protein vaccine lacking Montanide ISA-51.…”

“…7 However, the oily adjuvant Montanide ISA-51 is reported to provoke several adverse effects such us: Erythemas, itching and local pain at injection site. 4,8 Despite Montanide ISA-51 is a well-known adjuvant we hypothesized we can dispense of it since we are using VSSP. A recent study reveals that VSSP have the ability to activate mouse and human dendritic cells (DCs) in vitro and in vivo, with the corresponding IL-12p40/p70, TNFα and IL-6 production.…”

Toward a new generation of vaccines: The anti-cytokine therapeutic vaccines

“…Treatment of Castleman disease with anti-IL-6 Abs was transiently successful, but in this study, recurrence occurred after a few boosting injections (77). Active immunization against anti-IFN-␣ (65,66) and EGF (71) phase I trials, respectively, carried out in subjects infected with HIV-1 and in patients with malignant carcinomas including colon, lung, and prostate cancer, provided evidence for compliance, safety, and immunogenicity of the preparation. The immunogens used were formaldehyde-inactivated IFN-␣ and EGF coupled to tetanus toxoid and led to a dramatic rise of specific Abs.…”

“…Current vaccines have shown limitations in their use for diseases such as AIDS (65)(66)(67), allergies (76), and cancer (71,78). In these diseases, investigators have targeted exclusively the antigenic aggressor, be it a microbe, a cell, or an allergen, but not the cytokine immune dysregulation that the aggressor triggers.…”

Les kinoïdes

“…Les études précliniques réalisées avec les kinoïdes KLH-TNF-α humain, KLH-IL-4 humain et IFN-α humain inactivé (Antiferon ® ) [25] n'ont révélé chez la souris, le chien ou le singe aucune toxicité aiguë ou chronique. Au cours d'essais cliniques réalisés chez les patients atteints de cancers du côlon, de la prostate ou du sein, les vaccins anti-EGF ont été bien tolérés [30]. Dans le cadre de l'essai EURIS multicentrique de phase II/III réalisé en double aveugle sur 242 patients sidéens, l'immunisation par l'IFN-α inactivé (Antiferon ® ), qui a produit des titres élevés d'anticorps chez certains sujets, n'a révélé aucun effet collatéral infectieux ou autoimmun inhérent à l'immunisation pendant les 18 mois du suivi clinique [25].…”