Human CTL Epitopes Prostatic Acid Phosphatase-3 and Six-Transmembrane Epithelial Antigen of Prostate-3 as Candidates for Prostate Cancer Immunotherapy

Abstract

Specific immunotherapy of prostate cancer may be an alternative or be complementary to other approaches for treatment of recurrent or metastasized disease. This study aims at identifying and characterizing prostate cancerassociated peptides capable of eliciting specific CTL responses in vivo. Evaluation of peptide-induced CTL activity in vitro was done following immunization of HLA-A2 transgenic (HHD) mice. An in vivo tumor rejection was tested by adoptive transfer of HHD immune lymphocytes to nude mice bearing human tumors. To confirm the existence of peptide-specific CTL precursors in human, lymphocytes from healthy and prostate cancer individuals were stimulated in vitro in the presence of these peptides and CTL activities were assayed. Two novel immunogenic peptides derived from overexpressed prostate antigens, prostatic acid phosphatase (PAP) and sixtransmembrane epithelial antigen of prostate (STEAP), were identified; these peptides were designated PAP-3 and STEAP-3. Peptide-specific CTLs lysed HLA-A2.1 + LNCaP cells and inhibited tumor growth on adoptive immunotherapy. Furthermore, peptide-primed human lymphocytes derived from healthy and prostate cancer individuals lysed peptide-pulsed T2 cells and HLA-A2.1 + LNCaP cells. Based on the results presented herein, PAP-3 and STEAP-3 are naturally processed CTL epitopes possessing anti-prostate cancer reactivity in vivo and therefore may constitute vaccine candidates to be investigated in clinical trials. (Cancer Res 2005; 65(14): 6435-42)

Trogocytosis Is a Gateway to Characterize Functional Diversity in Melanoma-Specific CD8+ T Cell Clones

“…In vitro cytotoxicity assays were performed as described (17). Briefly, lymphocytes were washed, resuspended in complete medium, and mixed at different ratios with 5000 35 S-L-methionine-labeled melanoma or peptide-pulsed T2 cells.…”

STEAP1 is overexpressed in cancers: A promising therapeutic target

“…Given its increased expression in cancer tissues, STEAP1 could be a promising target for T-cell based or antibody immunotherapy. In prostate cancers, STEAP1-specific cytotoxic T lymphocytes (CTLs) were found to inhibit the growth of transplantable prostate tumor cells in murine models [2,4,5]. An immunization with recombinant DNA or modified vaccinia virus Ankara vector delivering STEAP1 antigen inhibited prostate cancer progression in a murine subcutaneous syngeneic tumor model [6].…”

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

“…These mice mount only HLA-A2.1-restricted CTL responses and were demonstrated as a useful biological tool for identifying potential TAA HLA-A2.1-restricted epitopes (Firat et al, 1999;Carmon et al, 2000;Machlenkin et al, 2005).…”