DELIVERY OF MUC1 MUCIN PEPTIDE BY POLY(D,L-LACTIC-CO-GLYCOLIC ACID) MICROSPHERES INDUCES TYPE-1 T-HELPER IMMUNE-RESPONSES

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 in jection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres con taining a MUC1 mucin peptide; It was hypothesized that microencapsulat ion of the MUC1 mucin peptide would prime for antigen-specific Th1 res ponses while avoiding the need for traditional adjuvants and carrier p roteins. Furthermore, a? 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 spe cific 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 i n interferon-gamma production. The antibody response was negative for IgM and IgG in the absence of MPLA; however, in the presence of MPLA a ntibody production was negative for IgM with a minimal IgG response co nsisting of IgG2a, IgG2b, and IgG3. Based on the antibody and cytokine profiles, it was concluded that MUC1 mucin peptide-loaded PLGA micros pheres are capable of eliciting specific Th1 responses, which may be e nhanced through the use of MPLA.