This consortium will determine whether improved clinical outcomes in patients with HER-2 breast cancer is correlated with strengthened immune CD4 T responses produced by monoclonal antibody treatment (Trastuzumab).
Anti-tumor antibody treatments have improved clinical outcomes for breast cancer and lymphoma patients. Researchers have thought that the monoclonal antibody breast cancer treatment Trastuzumab works by interfering with processes that regulate tumor growth. Animal model studies suggest that anti-tumor antibodies prevent tumor growth by inducing anti-tumor immune responses, but evidence of this has been lacking in human patients. Preliminary patient data from the collaborating investigators suggests this may be the case; those patients who experience a strong therapeutic effect from Trastuzumab are those who are developing their own antibody immune response to the target HER-2.
They now will determine whether Trastuzumab treatment induces significantly greater immune CD4 T cell responses and is associated with better clinical outcomes. They also will determine which innate immune cells stimulate the strengthened CD4 T cell attacks. Columbia and University of Miami researchers will enroll study participants. Even though the approximately 50 patients entered into the study will be treated with standard-of-care therapies in addition to Trastuzumab, the study is designed specifically to assess Trastuzumab’s effects. University of Miami and Columbia will provide the clinical testing resources, Mayo researchers will assess CD4 T cell responses, and Columbia researchers will study the antibody responses and the role of innate immune cells.
Significance: The study may provide direct evidence in breast cancer patients of immune responses stimulated by Trastuzumab, facilitating development of newer combination therapies designed to further strengthen these immune responses.