Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma

Abstract

We report on the design of a phase I, non-randomized, open-label study of idiotypic DNA vaccination in patients with B-cell non-Hodgkin's lymphoma (ISRCTN31090206). The study uses DNA fusion gene vaccination encoding patient-specific single chain variable fragment, or idiotype, linked to an immunostimulatory sequence. Two types of immunostimulatory sequence are being explored: potato virus X coat protein and human chemokine MIP3a. Linear polyethylenimine with low molecular weight (8 kDa) is used as a synthetic vehicle for vaccine delivery. Humoral and T-cellular immune responses to vaccination will be measured by ELISA and ELISPOT, respectively. The primary study endpoints are safety, tolerability and immunogenicity of DNA-PEI vaccination.

Polyethylenimine-based nanocarriers in co-delivery of drug and gene: a developing horizon

“…PEI cationic polymers have been widely investigated and used as carriers of non-viral gene carriers [25]. Due to its efficacy in facilitating cellular uptake and endosomal escape, which results in increased transfusion efficiency in both in vivo and in vitro, PEI has plenty of superficial positive charges and is able to condense negatively charge DNA into complexes that generate positive charge [26,27]. PEI with a molecular weight of 25 kDa (PEI25k) has been introduced as a ‘gold standard’ for gene carriers [27].…”

“…Due to its efficacy in facilitating cellular uptake and endosomal escape, which results in increased transfusion efficiency in both in vivo and in vitro, PEI has plenty of superficial positive charges and is able to condense negatively charge DNA into complexes that generate positive charge [26,27]. PEI with a molecular weight of 25 kDa (PEI25k) has been introduced as a ‘gold standard’ for gene carriers [27]. PEI can protect DNA from degradation in the endosomes/lysosomes compartment, due to the ‘proton sponge effect’ [28].…”

Targeting Head and Neck Cancer by Vaccination

“…Combination of DNA and EP induced durable antibody and T-cell responses in cancer patients ( 42 , 67 , 104 , 106 ). Other methods of DNA delivery including liposomes, tattooing and cationic polymers have also been also investigated ( 107 , 108 ).…”

Trial watch: DNA-based vaccines for oncological indications

“…An open-label, single-institution, randomized, Phase I clinical trial will enroll an estimate of 24 patients with Stage II/III triple-negative breast cancer, 260,261 who will receive standardof-care therapy followed by 6 intramuscular vaccinations targeting patient-specific tumor neoantigens (on days 1, 29 §7, 57 §7, 85 §7, 113 §7, and 141 §7) alone, or in combination with durvalumab 10 beginning at day 57 (NCT03199040). In addition, an open-label Phase I study using a similar approach will initially recruit 15 pancreatic cancer patients at 2 locations (Johns Hopkins School of Medicine, Baltimore, MD, USA and Washington University School of Medicine, St. Louis, MO, USA) to evaluate a personalized polyepitope DNA-based vaccine directed against patient-specific tumor neoantigens and MSLN 262 (NCT03122106).…”