Download Immunotherapy in Breast Cancer Kyong Hwa Park MD, PhD

Immunotherapy in Breast Cancer
Kyong Hwa Park MD, PhD
Division of Medical Oncology,
Department of Internal Medicine
Korea University College of Medicine
It has long been assumed that immune system plays important roles in eradication of tumors. In
recent years, development of molecular immunology provided more convincing data about
immune surveillance for cancer. Several studies have shown that immune signatures in the tumor
microenvironment have prognostic importance in a variety of cancers including breast cancer.
Moreover, studies have suggested that T cells found in high density within the tumor parenchyma
are also correlated with a survival benefit. Thus, breast cancers are considered to be immunogenic,
and multiple immunotherapeutic strategies are being tested as new clinical modalities which may
improve disease outcome.
Multiple tumor antigens have been identified for active immunotherapy in breast cancer patients:
MMTV antigen, carcinoembrionic antigen; CEA, mucin antigen, HER-2/neu, MAGE-1, and MAGE-3.
Immunotherapy of breast cancer can be categorized as either specific stimulation of the immune
system by active immunization, with cancer vaccines, or passive transfer of humor or cellular
materials, such as, tumor-specific antibodies or adoptive cell therapy that inhibit the function ofor directly kill tumor cells. Trastuzumab represents passive immunotherapy as monoclonal
antibodies, and has improved the survival of patients with human HER-2 over-expressing breast
cancer, in metastatic, locally advanced and resected subjects. Active immunization, in the form of
vaccines has been developed to target tumor antigens, and multiple different delivery platforms
including tumor cells, or their components, peptides, proteins, DNA, particles, such as viral or
viral-like or nanoparticles have been utilized. Data from clinical trials suggest that vaccines can
delay and prevent recurrence of breast cancer. However, there are several issues related to cancer
vaccine development; immune tolerance, lack of epitope display and escape from immune
response. Active research on the development of vaccines using multiple epitopes, that is resistant
to immune editing. Antigen-specific T cells can be generated in vitro and transferred to the
patients who have metastatic breast cancer. Small clinical trials have reported that adoptive T cell
therapy has produced long-term survivors. More recently, manipulations of the immune system, to
enhance the immune response and prevent its down-modulation, to induce killing of tumor cells
are under development. Prospects for improvement of treatment outcomes are proposals for
combining current modalities of immunotherapy with type 1 cellular immunity-inducing agents, all
targeting multiple tumor antigens.