Developing an effective breast cancer vaccine: challenges to achieving sterile immunity versus resetting equilibrium.
BACKGROUND
Evading immune destruction is an emerging hallmark of cancer. Immunotherapy of cancer is 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 (including immunomodulators) or adoptive cell therapy that inhibit the function of- or directly kill tumor cells. Modulation of immune response in cancer patients is the result of a balanced activity of T regulators and T effector cells.


RESULTS
We will present the current information and the prospects for the future of immunotherapy in patients with breast cancer including tumor antigens for vaccines and targets for monoclonal antibodies and adoptive T-cell therapy.


CONCLUSIONS
Active immunotherapy in breast cancer and its implementation into clinical trials has largely been a frustrating experience in the last decades. After many years of controversy, the concept that the immune system regulates cancer development is experiencing a new resurgence. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. It has been also clear that the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape.


CONCLUSIONS
What do we know about tumor immunogenicity and how might we therapeutically improve tumor immunogenicity? The first vaccine and the first immunomodulating agent were recently approved by the US Food and Drug Administration (FDA) for the treatment of prostate cancer (sipuleucel-T) and melanoma (ipilimumab), respectively. The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signalingsignaling pathways that regulate immune responses in the tumor microenvironment.
Early Drug Development for Innovative Therapies Division, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy. Electronic address: giuseppe.curigliano@ieo.it.
Giuseppe
G
Curigliano
Carmen
C
Criscitiello
Angela
A
Esposito
Luca
L
Fumagalli
Lucia
L
Gelao
Marzia
M
Locatelli
Ida
I
Minchella
Aron
A
Goldhirsch
D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D056747:Immunomodulation / Q000187:drug effects*; D016233:Immunotherapy, Active / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D020380:Needs Assessment; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000379:methods
D019496:Cancer Vaccines
Breast cancer; Immune modulation; Therapeutic vaccination