Identification of colon-tumor-associated antigens by T-cell lines derived from tumor-infiltrating lymphocytes and peripheral-blood lymphocytes from patients immunized with an autologous tumor-cell/bacillus Calmette-Guérin vaccine.
Tumor immunity developing as a response to an autologous colon-tumor/bacillus Calmette-Guérin (BCG) vaccine appears to be associated with induction of CD4+ helper T cells, implied by the observation that vaccine efficacy is associated with major histocompatibility complex class-II molecule expression on the vaccine tumor cells. Therefore, in an attempt to identify colon-tumor-associated antigens responsible for conferring immunity, we examined and compared the proliferative responses of peripheral-blood lymphocytes (PBL) from patients immunized with the autologous tumor/BCG vaccine to T-cell lines cloned expanded from colon-tumor-infiltrating lymphocytes to 5 antigens isolated on the basis of their reactivity by colon-tumor-reactive human monoclonal antibodies. Enzymatically dissociated colon tumors provided a source for establishment of cloned T-cell lines, tumor cell lines propagated in vitro or in vivo as nude-mouse xenografts and EBV-transformed B-cell lines used as antigen-presenting cells. Of 104 different T-cell lines tested, only 3 proliferated in response to CTAA 28A32-46K, and I to the CTAA28A32-32K antigen. In contrast, PBL from 64% of patients immunized with the autologous colon-tumor/BCG vaccine responded to the CTAA 28A32-32K antigen. This antigen is related to a family of calcium- and phospholipid-binding placental proteins termed annexins. Since proliferative responses developed to this antigen after vaccination in 64% of individuals, this antigen may be an important common colon-tumor-associated rejection antigen.
Ransom
J H
JH
Organon Teknika/Biotechnology Research Institute, Rockville, MD 20850.
Pelle
B A
BA
Hubers
H
H
Keynton
L M
LM
Hanna
M G
MG
Pomato
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D001500:BCG Vaccine / Q000008:administration & dosage*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002461:Cell Line, Transformed; D003110:Colonic Neoplasms / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D006023:Glycoproteins / Q000032:analysis; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D008214:Lymphocytes / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D006680:HLA Antigens; C030139:colon-specific antigen; C047052:tumor-associated antigen 72