Induction of long-lasting antitumor immunity by concomitant cell therapy with allogeneic lymphocytes and trifunctional bispecific antibody.
OBJECTIVE
Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD).


METHODS
A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or concomitantly with interleukin (IL)-2-activated (LAK) H-2(b) donor splenocytes to H-2(d/b) mice inoculated with murine melanoma cells transfected with human EpCAM.


RESULTS
A total of 32/38 mice treated with BiLu and LAK splenocytes, were tumor-free survivors without GVHD for >200 days following inoculation of a 100% lethal tumor dose (5 x 10(4)). Of 28 disease-free surviving mice previously treated with LAK splenocytes and BiLu, 24 mice proved resistance to a second tumor challenge of 10(4) cells given >210 days following the first tumor inoculation with no evidence of disease for >150 days. In contrast, only 4 of 13 disease-free survivor mice treated with naïve splenocytes and BiLu, and 5 of 10 disease-free survivor controls treated with BiLu only, resisted the second tumor challenge. Induction of antitumor immunity was more efficient and long-lasting (>150 days) in mice previously injected with a lethal tumor cell dose of 5 x 10(4) cells than in mice previously inoculated with 5 x 10(3) tumor cells.


CONCLUSIONS
Concomitantly treatment of allogeneic LAK cells and trAb-induced an efficient long-lasting antitumor immunity. Considering the documented efficacy of anti-EpCAM bispecific antibody in various metastatic cancers, clinical application of our approach may be justified in patients with minimal residual disease at high risk for tumor recurrence.
Morecki
Shoshana
S
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Laboratory, Hadassah University Hospital, Jerusalem, Israel. morecki@hadassah.org.il
Lindhofer
Horst
H
Yacovlev
Elena
E
Gelfand
Yael
Y
Ruf
Peter
P
Slavin
Shimon
S
D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003433:Crosses, Genetic; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D019076:Transgenes; D014184:Transplantation, Homologous
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D007376:Interleukin-2