T. Sato et al., DINITROPHENYL-MODIFIED AUTOLOGOUS MELANOMA VACCINE INDUCES A T-CELL RESPONSE TO HAPTEN-MODIFIED, MELANOMA PEPTIDES, Clinical immunology and immunopathology, 85(3), 1997, pp. 265-272
Active specific immunotherapy with dinitrophenyl (DNP)-modified autolo
gous melanoma vaccine elicits inflammatory responses in metastatic tum
or sites. Postsurgical adjuvant immunotherapy with this vaccine prolon
gs survival in stage III melanoma patients. We have reported that, aft
er administration of DNP-modified melanoma vaccine, T cell responses t
o DNP-modified autologous tumor cells are demonstrable in vivo and in
vitro. These responses are hapten specific and MHC restricted. To eluc
idate this phenomenon, we investigated the immune response to DNP-modi
fied peptides eluted from autologous cells. Short peptides were extrac
ted from DNP-modified and unmodified autologous melanoma cells by an a
cid elution technique and HPLC fractionation. Peptides were also extra
cted from DNP-modified and unmodified, EB virus-transformed, autologou
s B lymphoblasts. These various peptide fractions were loaded onto aut
ologous B lymphoblasts and tested for ability to elicit a response by
a DNP-specific T cell line as measured by IFN-gamma production. Unexpe
ctedly, stimulatory activity of peptides from DNP-modified melanoma ce
lls was confined to a single HPLC fraction. Spectrometric analysis of
this fraction confirmed modification of peptides with DNP. A weaker T
cell response was observed to a single HPLC fraction of DNP-modified p
eptides from the patient's B lymphoblasts. No T cell response was elic
ited by corresponding fractions of peptides eluted from unmodified mel
anoma cells or B lymphoblasts. These findings demonstrate the human T
cell response to DNP-modified autologous melanoma cells is mediated by
hapten-modified, MHC-associated peptides. Further investigation of th
ese peptides could lead to a new strategy for peptide-based cancer imm
unotherapy. (C) 1997 Academic Press.