Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma

Sci Rep. 2021 Nov 2;11(1):21427. doi: 10.1038/s41598-021-00787-5.

Abstract

A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus / genetics*
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Apoptosis
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cell Proliferation
  • Female
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Humans
  • Immunoglobulin Idiotypes / immunology*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Tumor Cells, Cultured
  • Vaccination / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Immunoglobulin Idiotypes