Olivera Finn

..Transgenic mouse models are providing encouraging indications of future usefulness of vaccines that are based on these molecules...

..In this review, we address main issues that have driven development of cancer vaccines and the challenges that have been met and/or are anticipated...

..This new immunology and pathology alliance named "Immunoscore" will advance research in both disciplines as well as benefit patients...

..g., high levels of MDSC) might already exist in some individuals, suggesting an even earlier premalignant stage or preselection of nonimmunosuppressed patients for prophylactic vaccination...

..Most exciting of all, these successes provide a rationale to expect that used in various combinations or earlier in disease, current and future immunotherapies may transform cancer treatment, improving a prognosis for many patients...

..A large number of outstanding young investigators, as well as several well-established tumor immunologists, were recruited to Pittsburgh at that time...

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..Considering how refractory cancer has been to standard therapy, efforts to achieve immune control of this disease are well justified...

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..At the very least, it should be given primary consideration in situations where the role of cytotoxic chemotherapy is equivocal and patients are in need of a nontoxic alternative...

..This suggests that the tumor-promoting microenvironment of chronic inflammation can be converted to a tumor-inhibiting environment by increasing adaptive immunity against a disease-associated antigen...

..We demonstrate that cyclin B1 vaccination delays spontaneous cyclin B1(+) tumor growth and increases median survival of tumor-bearing p53(-/-) mice...

..Reconstituted mice controlled the outgrowth of a MUC1-transfected but not the parental control tumor. scTCR expression appears lifelong, suggesting a successful transduction of the self-renewing stem cells...

..We found that cyclin B1 DNA prime-protein boost vaccine protected mice from a challenge with a tumor cell line that was established from a tumor arising in the p53(-/-) mouse that spontaneously overexpresses cyclin B1...

..In this review, we discuss the current efforts at designing and testing cancer vaccines in children with the focus on specific tumor antigens expressed by pediatric cancers...

..Collectively this work shows that it is possible to design vaccines based on tumor-associated antigens and elicit effective immunity against abnormal expression of these antigens on tumors without causing autoimmunity...

..Immune responses to aberrantly expressed cyclin B1 in tumors and premalignant lesions should be further explored as diagnostic and prognostic markers, in addition to their immunotherapeutic potential...

..We review evidence that the immune system recognizes some abnormally expressed cyclins as tumor antigens, such as cyclin B1, and we analyze the potential of cyclins D, E, and A to serve a similar function in cancer immunosurveillance...

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..We conclude that p53 plays an important role in cyclin B1 regulation and that tumors with mutated p53 will be good candidates for cyclin B1 based immunotherapy...

..Immunization of human MUC1 transgenic mice, where MUC1 is a self-antigen, with the VLP vaccine induced MUC1-specific CTL, delayed the growth of MUC1 transplanted tumors and elicited complete tumor rejection in some animals...

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..Further evaluation is warranted to examine the effect on disease-free survival and overall survival, especially in early disease and in the absence of immunosuppressive standard therapy...

..Our data suggest that the balance between Th and regulatory T cells is a critical parameter that could be modulated to improve the response to cancer vaccines...

..This represents an important consideration for designing safe and effective cancer vaccines...

..MUC1 is also expressed on pancreatic ductal epithelia. We tested the possibility that in IBD, MUC1 expression on pancreatic ducts is also abnormal leading to inflammation and pancreatitis...

..We conclude that MUC1 glycopeptides induce stronger immunity in MUC1-Tg mice because they are recognized as 'foreign' rather than ;self' and because they are cross-presented preferentially by DCs...

..Both scTCR and HSV-TK-EGFP genes were functional in the transduced cells, as evidenced by their specific recognition of MUC1(+) tumors and efficient eradication by ganciclovir...

..This chapter aimed to highlight some of these opportunities and to interest clinician scientists in exploring them in the near future...

..We discuss here some of the new therapeutic strategies for exploiting abnormal glycosylation pathways in tumors and using defined carbohydrate and/or glycoprotein tumor antigens in active specific immunotherapy of breast cancer...

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..Glycopeptides that are presented on DCs are recognized by T cells. This suggests that a much broader repertoire of T cells could be elicited against MUC1 and other glycoproteins than expected based only on their peptide sequences...

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..CONCLUSION: This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer...

..The concentration of MUC1 at the leading edge of polarized activated human T cells suggests that MUC1 could be involved in early interactions between T cells and endothelial cells at inflammatory sites...

..In this study, we examined whether the total number of ovulatory cycles decreases the likelihood of anti-MUC1 antibodies and provides an immune basis for the association between "incessant ovulation" and ovarian cancer risk...

..This can now be examined in relevant animal models, MUC1 and HLA transgenic mice that develop spontaneous MUC1 + tumors. ..

..Writing grant proposals to various private and government funding agencies; 3. Teaching in courses related to their field of expertise. ..

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..In this renewal application, work will be done to show that this form of immunotherapy and the same vaccines may be useful not only for cancer but also for treatment and prevention of chronic inflammations that increase risk for cancer. ..

..The long term goals of the project are to fully understand the anti-tumor mucin response and its potential for immunotherapy...

..In vivo correlates to these experiments will be performed in C57BL/6 and C57BL/6-MUC-1 transgenic mice. ..

..Nobody has yet considered MUC1 as a target for therapy, and specifically immunotherapy, of chronic inflammatory diseases that carry increased risk of cancer. ..