Chapter category: Vaccines
Studies of MUC1 Peptides
Peptide-Based Cancer Vaccines
Edited by: W. Martin KastISBN: 1-58706-026-4
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Chapter authors:
Vasso Apostolopoulos, Geoffrey A. Pietersz and Ian FC McKenzie
There have been more studies of Mucin 1 (MUC1) peptides in breast cancer than of any other peptides in this disease, and it is appropriate that the use of MUC1 peptides and vaccines be reviewed here. In contrast to melanoma peptides (discussed elsewhere), where the peptide epitopes were defined by CTLs at the beginning of the studies, mucin peptides were examined for different reasons. Firstly, there is a great increase in mucins- up to 100 fold in cancers, compared to normal tissues, and therefore could provide an appropriate target for the differential activity of CTLs.1 Thus, if the increase in total amount of mucins is reflected with an increased amount of peptide presented by Class I molecules, then CTLs would be 100 times more effective against cancer than against normal tissues; whether this is so remains to be seen. Secondly, there is much information available on MUC1 and its peptides; MUC1 was the first mucin to be cloned and the protein structure deduced, it is a large cell surface molecule which, by definition, is highly O-glycosylated and therefore contains many serine, threonine and proline residues. Of interest, not only for MUC1, but for all the mucins (MUC1-8 described thus far) is a 20 amino acid repeat in the extracellular region (the VNTR), and for MUC1 it is repeated up to 40 times in different alleles.1 Thirdly, MUC1 is an attractive molecule for immunological studies, it is highly immunogenic in mice, shown initially by immunizing mice with human cancers to make monoclonal antibodies, when almost all antibodies were found to react with the highly immunogenic VNTR, indeed with the APDTR amino acids within this region.2,3 This immunogenicity in mice would not be of great interest or relevance other than for Olja Finn's findings that the lymph nodes of patients with breast cancer contains cells that could be stimulated to give non-MHC restricted CTLs.4 While the in vivo relevance of these unusual CTLs is not known in protecting patients against cancer, these studies were of great importance as they galvanized breast cancer “vaccinologists” into using MUC1 as a potential vaccine and preceded other studies using MUC1 peptides in breast cancer. However, such non- restricted cells cannot be lightly dismissed, clearly they are specifically selected (while MHC restricted cells are selected against) in their mode of identification, by re- stimulating with different MUC1+ cell lines with different HLA phenotypes. However, it is of interest that a patient with breast cancer later became pregnant (MUC1 is greatly increased in the lactating breast) and had a severe case of mastitis accompanied with heavy lymphocyte infiltration, a high frequency of CTLs to MUC1 and there has been no recurrence of the cancer; it is possible that the non-MHC restricted cells were protective (see below).5
Additional chapters from this book:
Melanoma Peptide Clinical Trials
Ian D. Davis and Michael T. Lotze
Although various immunologic approaches to the treatment of cancer have been used for over a century,1 it is only relatively recent that specific human cancer targets have been defined allowing spec...
Gp100 and G250: Towards Specific Immunotherapy Employing Dendritic Cells in Melanoma and Renal Cell Carcinoma
Joost L.M.Vissers, I. Jolanda M. de Vries, Egbert Oosterwijk, Carl G. Figdor and Gosse J. Adema
A long history of studies demonstrate the capacity of the immune system to develop specific reactivity against antigens foreign to the host, like viral and bacterial antigens. During the last decade...
Peptide Vaccines for the Treatment of Melanoma
Willem W. Overwijk and Nicholas P. Restifo
The development of cancer vaccines has been greatly advanced by the recent identification of many tumor-associated antigens (TAA) recognized by T cells.1,2 A majority of these antigens have been clo...
Peptides in Cervical Cancer
Maaike E. Ressing, Remco M.P. Brandt, Joan H. de Jong, Rienk Offringa, Cornelis J.M. Melief and W. Martin Kast
Observations that susceptibility to several cancer types is increased in immunocompromised individuals have led to the assumption that immune responses are able to interfere with tumor development.1...
Peptides in Prostate Cancer
Michael L. Salgaller
The timely detection and effective treatment of prostatic cancer is one of the major health problems faced in the United States and, to a comparable extent, the rest of the world. It is predicted th...
Clinical Trials of HER-2/neu Peptide-Based Vaccines
Mary L. Disis and Martin A. Cheever
Cancer vaccines are not used routinely in the clinical practice of most oncologists, despite decades of study. Several advances in basic immunology over the last few years have forced a re-evaluatio...
Cytotoxic T Cell Epitopes and Tissue Distribution of the HER-2/neu Proto-Oncogene: Implications for Vaccine Development
Barbara Seliger, Koji Kono, Y. Rongcun and Rolf Kiessling
The development of immunotherapeutic methods to treat cancer is critically depen dent on the identification of tumor-associated antigens (TAA). Several immunodominant peptide epitopes, recognized by...
Studies of MUC1 Peptides
Vasso Apostolopoulos, Geoffrey A. Pietersz and Ian FC McKenzie
There have been more studies of Mucin 1 (MUC1) peptides in breast cancer than of any other peptides in this disease, and it is appropriate that the use of MUC1 peptides and vaccines be reviewed here...
Carcinoembryonic Antigen (CEA) Peptides and Vaccines for Carcinoma
Jeffrey Schlom
This Chapter addresses the current status of the development of recombinant vaccines employing carcinoembryonic antigen (CEA) as the target antigen. Included is an over view of preclinical studies a...
Cancer Peptide Vaccines in Clinical Trials
Jeffrey S. Weber
The revelation that protein antigens were processed into peptides by a pathway of intracellular degradation and presented on the surface of antigen presenting cells for recognition by T-cells in ass...
Critical Dependence of the Peptide Delivery Method on the Efficacy of Epitope Focused Immunotherapy
Gregory E. Holt, Markwin P. Velders, Michael P. Rudolf, Laurie A. Small, Maurizio Provenzano, Sanne Weijzen, Diane M. Da Silva, Marten Visser, Simone A.J. ter Horst, Remco M.P. Brandt and W. Martin Kast
Tumor immunotherapy describes the use of the immune system as a tool to eliminate cancer from the stricken patient. The theory contends that immunization against certain proteins either associated w...
p53: A Target for T-Cell Mediated Immunotherapy
Michel P.M. Vierboom, Dmitry I. Gabrilovich, Rienk Offringa, W. Martin Kast and Cornelis J.M. Melief
Burnet’s theory of immunosurveillance postulates that malignant transformation causes the expression of neoantigens. The theory states tumor specific antigens are recognized by the immune system, ...
Mutant Oncogene and Tumor Suppressor Gene Products and Fusion Proteins Created by Chromosomal Translocations as Targets for Cancer Vaccines
V. Ellen Maher, B. Scott Worley, David Contois, M. Charles Smith, Michael J. Kelley, Michael Stipanov, Samir N. Khleif, Theresa Goletz, Leon van den Broeke, Crystal Mackall, Lee J. Helman, David P. Carbone and Jay A. Berzofsky
Identification and Selection of T-Cell Epitopes Derived from Tumor-Associated Antigens for the Development of Immunotherapy for Cancer
Esteban Celis
Because the immune system has the capacity to recognize and in many cases destroy tumor cells, significant efforts are being devoted to the development of immune-based therapies for cancer. Both cyt...
