Induction of adaptive Anti-HER2/neu immune responses in a Phase 1B/2 trial of 2B1 bispecific murine monoclonal antibody in metastatic breast cancer (E3194): a trial coordinated by the Eastern Cooperative Oncology Group.
2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the FcgammaRIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2B1 therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but 1 patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate antibody-directed cellular cytotoxicity may exert their clinical antitumor effects.
Borghaei
Hossein
H
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Alpaugh
R Katherine
RK
Bernardo
Patricia
P
Palazzo
Irma E
IE
Dutcher
Janice P
JP
Venkatraj
Usha
U
Wood
William C
WC
Goldstein
Lori
L
Weiner
Louis M
LM
D000328:Adult; D000368:Aged; D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy*; D019496:Cancer Vaccines; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000295:instrumentation* / Q000379:methods*; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D016207:Cytokines; D018719:Erb-b2 Receptor Tyrosine Kinases