Author(s): Lijin Li aff1 , S Peter Goedegebuure aff1 aff2 , Timothy P Fleming aff1 aff2 , William E Gillanders [*] aff1 aff2
breast cancer; clinical trial; DNA vaccine; immunotherapy; mammaglobin-A
Breast cancer is the most common cancer and is second only to lung cancer as the leading cause of cancer death among American women. The latest Cancer Facts & Figures 2015 [1 ] estimates that 231,840 new cases of invasive breast cancer will be diagnosed in 2015, representing 29% of all new cancer cases among women in the USA. Although the number of deaths from breast cancer has declined in recent years, 40,290 women are predicted to die of breast cancer in 2015 [ 1 ]. Clearly, innovative strategies for breast cancer prevention and therapy must be considered a public health priority.
Cancer vaccine therapy
It has long been known that there is a dynamic relationship between the immune system and cancer. This dynamic relationship has been studied in detail, ultimately resulting in the establishment of the cancer immunoediting concept [2 ]. Evading immune destruction has been recognized as an emerging hallmark of cancer [3 ]. Recent successes in cancer immunotherapy have highlighted the importance of the immune system in controlling cancer, and cancer immunotherapy was identified by Science magazine as the 2013 breakthrough of the year [4 ]. Both immune checkpoint blockade (anti-CTLA-4 and anti-PD-1) therapy and chimeric antigen receptor therapy have demonstrated spectacular results in clinical trials [5,6 ].
These dramatic successes in cancer immunotherapy have renewed interest in cancer vaccine therapy [7 ]. Cancer vaccines are typically designed to stimulate the immune system to mount a cell-mediated immune response against one or more tumor-associated antigens. Cancer vaccines have excellent safety profiles and several have now received US FDA approval including Gardasil and Cervarix for prevention of cervical cancer and Provenge for treatment of metastatic prostate cancer. Investigators are now pursuing several different cancer vaccine platforms including autologous cellular vaccines, DNA vaccines and protein or peptide vaccines, often in combination with conventional cancer treatment regimens. We recently completed an open-label Phase I clinical trial (Clinicaltrials.gov identifier: NCT00807781) evaluating the safety and immunogenicity of a DNA vaccine designed to express the human breast cancer-associated mammaglobin-A antigen. Results of the trial demonstrate the safety of the mammaglobin-A DNA vaccine, with preliminary evidence to suggest that the mammaglobin-A vaccine is able to induce mammaglobin-A-specific IFN-[gamma]-secreting CD8 T cells in treated patients. These patients also had improved progression-free survival [8 ].
Mammaglobin-A is an exceptional target for breast cancer vaccine therapy
Mammaglobin-A is a member of the secretoglobin superfamily (family 2A member 2). The mammaglobin-A gene (SCGB2A2) was first identified using a differential screening approach directed at the isolation of novel human breast cancer-associated genes [9 ]. Since its original identification, mammaglobin-A has proven to be an important molecular marker for the detection of metastatic breast cancer, and it has been the focus of over 300 publications in the medical literature. The exquisite tissue specificity and near universal overexpression of mammaglobin-A makes it an...