Cancer Vaccines

Publication Title: 
International Journal of Oncology

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined.

Author(s): 
Ojima, Toshiyasu
Iwahashi, Makoto
Nakamura, Masaki
Matsuda, Kenji
Nakamori, Mikihito
Ueda, Kentaro
Naka, Teiji
Katsuda, Masahiro
Miyazawa, Motoki
Yamaue, Hiroki
Publication Title: 
Human Vaccines

Cancer carbohydrate antigens have been surprisingly potent targets for immune recognition and attack by antibodies, both because of their abundance at the cell surface and their immunogenicity. Antibodies are ideally suited for eradicating pathogens from the bloodstream and from early tissue invasion. Passively administered and vaccine induced antibodies have accomplished this, eliminating circulating tumor cells and systemic or intraperitoneal micrometastases in a variety of preclinical models.

Author(s): 
Livingston, Philip O.
Ragupathi, Govind
Publication Title: 
Vaccine

BACKGROUND: Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c.

Author(s): 
Ragupathi, Govind
Yeung, K. Simon
Leung, Ping-Chung
Lee, Mavis
Lau, Clara Bik San
Vickers, Andrew
Hood, Chandra
Deng, Gary
Cheung, Nai-Kong
Cassileth, Barrie
Livingston, Philip
Publication Title: 
Cancer Immunity

A differentiation antigen commonly expressed on melanoma cells, gp100 is the target of infiltrating T cells. We conducted a phase I randomized cross-over trial of melanoma patients with either xenogeneic (mouse) or human gp100 plasmid DNA injected intramuscularly at three dosages (100, 500 or 1,500 microg) every three weeks for three doses. After the first three injections, patients were then immunized three times with gp100 from the other species.

Author(s): 
Yuan, Jianda
Ku, Geoffrey Y.
Gallardo, Humilidad F.
Orlandi, Francesca
Manukian, Gregor
Rasalan, Teresa S.
Xu, Yinyan
Li, Hao
Vyas, Shachi
Mu, Zhenyu
Chapman, Paul B.
Krown, Susan E.
Panageas, Katherine
Terzulli, Stephanie L.
Old, Lloyd J.
Houghton, Alan N.
Wolchok, Jedd D.
Publication Title: 
Vaccine

The saponin fraction QS-21 from Quillaja saponaria has been demonstrated to be a potent immunological adjuvant when mixed with keyhole limpet hemocyanin conjugate vaccines, as well as with other classes of subunit antigen vaccines. QS-21 adjuvant is composed of two isomers that include the apiose and xylose forms in a ratio of 65:35, respectively. The chemical syntheses of these two isomers in pure form have recently been disclosed. Herein we describe detailed in vivo immunological evaluations of these synthetic QS-21 isomeric constituents, employing the GD3-KLH melanoma antigen.

Author(s): 
Ragupathi, Govind
Damani, Payal
Deng, Kai
Adams, Michelle M.
Hang, Jianfeng
George, Constantine
Livingston, Philip O.
Gin, David Y.
Publication Title: 
Planta Medica

The 95 % ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids.

Author(s): 
Hong, Feng
Xiao, Weilie
Ragupathi, Govind
Lau, Clara B. S.
Leung, Ping Chung
Yeung, K. Simon
George, Constantine
Cassileth, Barrie
Kennelly, Edward
Livingston, Philip O.
Publication Title: 
Cancer immunology, immunotherapy: CII

BACKGROUND: Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies, such as ipilimumab, have generated measurable immune responses to Melan-A, NY-ESO-1, and gp100 antigens in metastatic melanoma. Vaccination against such targets has potential for immunogenicity and may produce an effector-memory T-cell response.

Author(s): 
Yuan, Jianda
Ginsberg, Brian
Page, David
Li, Yanyun
Rasalan, Teresa
Gallardo, Humilidad F.
Xu, Yinyan
Adams, Sylvia
Bhardwaj, Nina
Busam, Klaus
Old, Lloyd J.
Allison, James P.
Jungbluth, Achim
Wolchok, Jedd D.
Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available.

Author(s): 
Bertino, Pietro
Panigada, Maddalena
Soprana, Elisa
Bianchi, Valentina
Bertilaccio, Sabrina
Sanvito, Francesca
Rose, Aaron H.
Yang, Haining
Gaudino, Giovanni
Hoffmann, Peter R.
Siccardi, Antonio
Carbone, Michele
Publication Title: 
Human Gene Therapy

Thirty-three metastatic melanoma patients were vaccinated according to a phase I-II study with an allogeneic melanoma cell line that was genetically modified by transfection with a plasmid containing the gene encoding human interleukin 2 (IL-2). The cell line expresses the major melanoma-associated antigens and the HLA class I alleles HLA-A1, -A2, -B8, and Cw7. All patients shared one or more HLA class I alleles with this cell line vaccine.

Author(s): 
Osanto, S.
Schiphorst, P. P.
Weijl, N. I.
Dijkstra, N.
Van Wees, A.
Brouwenstein, N.
Vaessen, N.
Van Krieken, J. H.
Hermans, J.
Cleton, F. J.
Schrier, P. I.
Publication Title: 
Current Opinion in Immunology

Following vaccination with defined tumor antigens that are recognized by T cells, a small proportion of cancer patients display tumor regressions. Several reports describe anti-vaccine T-cell responses, evaluated with a variety of methods, for example, by assessing T-cell function or expression of specific TCR. However, a correlation between these T-cell responses and the tumor regressions has not yet been established. It appears that some patients display tumor regression with an unexpectedly low frequency of anti-vaccine T cells.

Author(s): 
Coulie, Pierre G.
van der Bruggen, Pierre

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