Journal
JOURNAL OF IMMUNOLOGICAL METHODS
Volume 248, Issue 1-2, Pages 183-194Publisher
ELSEVIER
DOI: 10.1016/S0022-1759(00)00351-3
Keywords
Fc receptor (CD64); prostate specific antigen; MHC class I; antigen presentation; cross-priming
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Funding
- NCI NIH HHS [CA-23108] Funding Source: Medline
- NIAID NIH HHS [AI19053] Funding Source: Medline
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Vaccine therapy is attractive for prostate cancer patients because the tumor is slow growing (allowing time to augment host responses) and occurs in an older population less likely to tolerate more toxic treatments. We have constructed an expression vector based on a monoclonal antibody (mAb) that targets the high affinity receptor for IgG (Fc gamma RI, CD64) which is exclusively expressed on myeloid cells including dendritic cells (DC). The heavy chain of mAb H22 CH2 and CH3 domains were removed and replaced with the gene for prostate specific antigen (PSA). Using that vector, we have constructed and purified FPH22.PSA, a fusion protein that targets PSA to Fc gamma RI on antigen presenting cells (APC). This fusion protein has an apparent molecular mass of 80-83 kDa, binds to Fc gamma RI with high affinity and expresses PSA. We demonstrate that FPH22.PSA targeted PSA was internalized and processed by the human myeloid THP-I cell line resulting in presentation of MHC class I-associated PSA peptides and lysis of THP-1 by PSA-specific human CTL. Moreover, pretreatment of THP-I cells with antibodies to block either Fc gamma RI or MHC class I, blocked lysis indicating that targeting to Fc gamma RI results in presentation of exogenous antigen on MHC class I molecules. These data demonstrate that FPH22.PSA was processed in such a manner by the myeloid cell line to allow for presentation of immunodominant peptides in MHC class I molecules and suggests that uptake of antigen via Fc gamma RI results in cross-priming. (C) 2001 Elsevier Science BN. All rights reserved.
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