Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses

J Pharm Sci. 1998 Nov;87(11):1421-7. doi: 10.1021/js980070s.

Abstract

Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hypothesized that microencapsulation of the MUC1 mucin peptide would prime for antigen-specific Th1 responses while avoiding the need for traditional adjuvants and carrier proteins. Furthermore, an immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the peptide-loaded PLGA microspheres based on its ability to enhance Th1 responses. The results revealed T cell specific immune responses. The cytokine secretion profiles of the T cells consisted of high levels of interferon-gamma with undetectable levels of interleukin-4 and interleukin-10. Moreover, incorporation of MPLA in the MUC1 peptide-loaded PLGA microspheres resulted in an increase in interferon-gamma production. The antibody response was negative for IgM and IgG in the absence of MPLA; however, in the presence of MPLA antibody production was negative for IgM with a minimal IgG response consisting of IgG2a, IgG2b, and IgG3. Based on the antibody and cytokine profiles, it was concluded that MUC1 mucin peptide-loaded PLGA microspheres are capable of eliciting specific Th1 responses, which may be enhanced through the use of MPLA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Carriers
  • Drug Delivery Systems*
  • Female
  • Lactic Acid*
  • Mice
  • Mice, Inbred C57BL
  • Microspheres
  • Molecular Sequence Data
  • Mucin-1
  • Oligopeptides / administration & dosage*
  • Oligopeptides / immunology
  • Peptide Fragments
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Drug Carriers
  • MUC1 tandem repeat peptide
  • Mucin-1
  • Oligopeptides
  • Peptide Fragments
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid