To be able to detect very early tumors, or even premalignant lesions, a diagnostic screening test must be very sensitive and specific. One promising approach to the early detection of cancer is to look, not for proteins secreted by the cancer, but for an antibody immune response to cancer. The advantage of using antibody immunity as an early marker of cancer is that the immune system can respond to immunogenic proteins at low levels that would not be detectable by direct protein screening. In addition, the immune system can potentially detect subtle alterations in proteins when they become aberrantly expressed or mutated in cancer. Serum antibodies to tumor associated proteins have been shown to be useful biomarkers for a variety of cancers.
Cancers can express abnormal levels of mutated or modified forms of proteins associated with malignant growth. Such proteins can be detected by our immune system and elicit subsequent cellular and humoral immune responses. There is much published evidence that serum antibodies recognizing tumor associated antigens can be detected in cancer patients. This evidence supports the idea of using serum antibodies to tumor antigens as biomarkers for cancer diagnosis. The advantage of using antibody immunity as an early marker of cancer is that the immune system can respond to immunogenic proteins at low levels that would not be readily detectable by direct protein screening. As each antibody marker is only present in a limited proportion of patients, usually less than 20%, a combination of biomarkers that defines the immunological signature of cancer needs to be developed.
The identification of an immunological signature of cancer depends on the availability high-throughput screening technologies. Recent advances in protein array technology that allows for simultaneous evaluation of serum antibody responses to thousands of proteins immobilized on chips has revolutionized the field of serum antibody profiling. Moreover, screening patient serum against cDNA expression libraries has also proven to be a high throughput method of tumor specific antibody identification. Using combinatorial approaches for biomarker discovery, we aim to define antibody panels that would be useful in the diagnosis of many common cancers. We have made substantial progress in identifying an immunologic signature in breast, ovarian, and colon cancers.
Immune diagnostics from laboratory to clinic
- Our group has demonstrated that HER2/neu (HER2) antibody immunity can be detected in early stage breast cancer patients and is positively correlated with overexpression of the HER2 protein by the tumor. We have also found that breast cancer patients have increased antibody immunity to other proteins expressed in their tumors.
- Tumor Vaccine Group scientists have identified a multitude of biologically relevant antigens in a variety of tumor types including breast, ovarian, colon, and lung cancer.
- We have demonstrated that antibody immunity to multiple antigens expressed in ovarian cancer, particularly p53, is associated with an improved overall survival.
- We have developed several high throughput screening techniques that have allowed rapid identification and analysis of potential tumor associated antibody markers for early detection, diagnosis, and prognosis assessment in several cancers.
- Ongoing early stage and validation studies in a variety of cancer types.
We will continue to develop panels of biomarkers for cancer detection and are actively looking for collaborators with well characterized sera banks that would be interested in working with us on these projects. We have significant efforts in technology development in this area continuing with refining further high throughput techniques for discovery validation. We are beginning to explore the nature of endogenous tumor specific antibodies and their role in inhibiting or accelerating tumor growth. Finally, antigens identified are being exploited therapeutically by scientists working on other programs of the Cancer Vaccine Institute.