PMID- 9811500 OWN - NLM STAT- MEDLINE DCOM- 19981223 LR - 20181201 IS - 0022-3549 (Print) IS - 0022-3549 (Linking) VI - 87 IP - 11 DP - 1998 Nov TI - Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses. PG - 1421-7 AB - 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. FAU - Newman, K D AU - Newman KD AD - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton Alberta, Canada. FAU - Sosnowski, D L AU - Sosnowski DL FAU - Kwon, G S AU - Kwon GS FAU - Samuel, J AU - Samuel J LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pharm Sci JT - Journal of pharmaceutical sciences JID - 2985195R RN - 0 (Drug Carriers) RN - 0 (MUC1 tandem repeat peptide) RN - 0 (Mucin-1) RN - 0 (Oligopeptides) RN - 0 (Peptide Fragments) RN - 0 (Polymers) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) SB - IM MH - Amino Acid Sequence MH - Animals MH - Drug Carriers MH - *Drug Delivery Systems MH - Female MH - *Lactic Acid MH - Mice MH - Mice, Inbred C57BL MH - Microspheres MH - Molecular Sequence Data MH - Mucin-1 MH - Oligopeptides/*administration & dosage/immunology MH - Peptide Fragments MH - *Polyglycolic Acid MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - *Polymers MH - T-Lymphocytes, Helper-Inducer/*immunology EDAT- 1998/11/13 03:02 MHDA- 2000/07/19 11:00 CRDT- 1998/11/13 03:02 PHST- 1998/11/13 03:02 [pubmed] PHST- 2000/07/19 11:00 [medline] PHST- 1998/11/13 03:02 [entrez] AID - S0022-3549(15)50687-4 [pii] AID - 10.1021/js980070s [doi] PST - ppublish SO - J Pharm Sci. 1998 Nov;87(11):1421-7. doi: 10.1021/js980070s.