CYCLIN B1 IN IMMUNOTHERAPY, DIAGNOSIS, AND PROGNOSIS OF LUNG CANCER

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Linked publications, trials & patents

Abstract

Aberrant expression of cell cycle regulatory proteins characterizes many human tumors, including lung[unreadable] cancer. Dysregulated expression of cyclin B1 (CB1), demonstrated by constitutive overexpression and[unreadable] mislocalization in the cytoplasm rather than the nucleus, is especially significant because it contributes to[unreadable] malignant transformation and increased metastatic potential of tumor cells. Aberrant expression of CB1 is a[unreadable] result of functional inactivation of the tumor suppressor gene p53, an early event in the progression from[unreadable] premalignant to malignant lesions in the lung, suggesting that it could be a marker and a potential target in[unreadable] early as well as late stage cancer. CB1 overexprression in lung cancer elicits specific antibodies and T cells.[unreadable] CB1-specific antibodies are also seen in heavy smokers who are at high risk for developing lung cancer.[unreadable] Experiments, in mice show that anti-CB1 specific immune responses can protect from tumor challenge. The[unreadable] first hypothesis to be tested in Project 2 is that vaccines will elicit or boost CB1-specific immunity in[unreadable] lung cancer patients and that will result in an anti-tumor effect. Our second hypothesis is that the[unreadable] immune response against CB1 could be a biomarker of risk for development of future lung cancer in[unreadable] subjects with a positive smoking history or for recurrence among early-stage patients newly[unreadable] diagnosed with lung cancer. These two hypotheses are being tested in three specific aims. In Specific[unreadable] Aim 1 we propose to carry out clinical trials testing CB1 vaccines safety and immunogenicity in stage I and II[unreadable] lung cancer patients undergoing tumor resection. In Specific Aim 2 we will analyze and compare the[unreadable] quantitative and qualitative features of anti-cyclin B1 immunity in cancer patients and high-risk individuals in[unreadable] an attempt to elucidate important immune correlates of protection. In Specific Aim 3 we propose to evaluate[unreadable] the diagnostic and prognostic value of anti-CB1 antibodies in high risk individuals and cancer patients and to[unreadable] compare it to other diagnostic and prognostic markers studied in the SPORE projects. The overall goal is to[unreadable] translate the new knowledge acquired in the past grant period on the mechanisms of CB1 dysregulation and[unreadable] anti-CB1 immunity, to diagnosis, prognosis and therapy of lung cancer.[unreadable]