- Email: [email protected]
Cancer vaccines in the new era of cancer immunotherapy
G Model
ARTICLE IN PRESS
JVAC 16962 1
Vaccine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Editorial
Cancer vaccines in a new generation of cancer immunotherapy
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After over a century of study, it is now well established that malignancies, both microbial- and non-microbial-initiated malignancies, are naturally recognized and attacked by the immune system. Despite recognition by the immune system, however, cancers develop escape mechanisms such as antigen-loss and local immunosuppression that enable them to resist the immune attack. Thus, effective immunotherapies depend on strategies that can generate immune effectors that can overcome these problems. Immunotherapy is rapidly becoming a primary choice of cancer therapy with federal licensing of several approaches over the last decade including cytokines, vaccines, and monoclonal antibody therapies, used alone or in conjunction with other approaches (e.g. chemotherapy). Because of their prominent societal role in safely and effectively decreasing morbidity and mortality associated with infectious diseases, there has been considerable interest in developing the use of vaccines for cancers. However, this is one facet of immune therapies that has yet to succeed with the exception of vaccines that prevent entry of and infection by cancer causing microbes such as Hepatitis B Virus and Human Papilloma Virus. There have been many, sporadic efforts over the last 100 years to develop the clinical use of vaccine for a wide spectrum of cancer. However, in the past two decades there have been more consistent efforts to develop and apply cancer vaccines therapeutically and preventively, consistently building on our rapidly changing understanding of the immune system in higher organisms. In the traditional sense, vaccines contain at least two components, antigens that can be recognized by the adaptive immune system (i.e. T and B cells) and an adjuvant that serves as a danger signal to activate the adaptive immune response. Most of us think of vaccines as useful to prevent infections before they occur, like measles and influenza. Indeed, there are now cancer vaccines, such as Gardasil and Cervarix that prevent HPV infections, a leading cause of cervical and head and neck cancers. However, cancer vaccines may also be therapeutic, albeit likely in combination with other approaches that mitigate immune escape. As with any vaccine, there are multiple ways to provide antigen or adjuvant and to administer vaccine. These include not only typical approaches of direct injection of antigen, but also include newer strategies that augment the response to local antigen that is released into the tumor microenvironment under acute inflammatory conditions, including localized radiation and monoclonal antibody therapy (e.g. trastuzumab). Additionally, our understanding of immunologic tolerance is fostering development of designer antigens that eliminate regions recognized by dominant peripheral Treg-mediated tolerance mechanisms.
New approaches that exploit recently defined principles of molecular and cellular immunobiology combined with an expanded ability to monitor the immune response have accelerated clinical application of immunotherapy and vaccines for cancer. Furthermore, the practicing oncology community has begun, in earnest, increasing its focus on ushering immunotherapy into mainstream therapeutics of cancer. Large pharmaceutical companies are rapidly expanding their cancer immunotherapy portfolios by investing in tumor immunotherapy development and acquiring technologies from smaller biotechnology companies. Currently, there are many promising immunotherapies that have or are working their way through clinical trials and FDA registration that could in effect be considered a vaccine or an important component of a vaccine strategy. Prominent examples include new approved treatments that target the CTLA-4 and PD-1 immunologic checkpoints which can be viewed as novel immunologic adjuvants when combined with traditional antigen formulations. Vaccine is the pre-eminent journal for publishing articles related to vaccines and vaccination for infectious disease, cancers and other pathologic conditions. In this first part of a Special Edition of Vaccine focusing on cancer, we are pleased to present a collection of review articles from prominent immunotherapy experts that broadly cover several timely issues related to the ongoing interest of developing cancer vaccines. Keith L. Knutson ∗ Q1 Department of Immunology, Mayo Clinic, Jacksonville, FL, United States Q2 Elizabeth A. Mittendorf Department of Breast Surgical Oncology, MD Anderson Cancer Center, Houston, TX, United States ∗ Corresponding author at: Mayo Clinic Center for Immunology and Immune Therapies, Department of Immunology, Mayo Clinic Florida, Griffin Building, 251B, 4500 San Pablo Rd., Jacksonville, FL 32224, United States. Tel.: +1 904 953 6657. E-mail address: [email protected] (K.L. Knutson)
Available online xxx
http://dx.doi.org/10.1016/j.vaccine.2015.09.086 0264-410X/© 2015 Published by Elsevier Ltd.
Please cite this article in press as: Knutson KL, Mittendorf EA. Cancer vaccines in a new generation of cancer immunotherapy. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.09.086
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86
ARTICLE IN PRESS
JVAC 16962 1
Vaccine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Editorial
Cancer vaccines in a new generation of cancer immunotherapy
1
2
3
Q3
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
After over a century of study, it is now well established that malignancies, both microbial- and non-microbial-initiated malignancies, are naturally recognized and attacked by the immune system. Despite recognition by the immune system, however, cancers develop escape mechanisms such as antigen-loss and local immunosuppression that enable them to resist the immune attack. Thus, effective immunotherapies depend on strategies that can generate immune effectors that can overcome these problems. Immunotherapy is rapidly becoming a primary choice of cancer therapy with federal licensing of several approaches over the last decade including cytokines, vaccines, and monoclonal antibody therapies, used alone or in conjunction with other approaches (e.g. chemotherapy). Because of their prominent societal role in safely and effectively decreasing morbidity and mortality associated with infectious diseases, there has been considerable interest in developing the use of vaccines for cancers. However, this is one facet of immune therapies that has yet to succeed with the exception of vaccines that prevent entry of and infection by cancer causing microbes such as Hepatitis B Virus and Human Papilloma Virus. There have been many, sporadic efforts over the last 100 years to develop the clinical use of vaccine for a wide spectrum of cancer. However, in the past two decades there have been more consistent efforts to develop and apply cancer vaccines therapeutically and preventively, consistently building on our rapidly changing understanding of the immune system in higher organisms. In the traditional sense, vaccines contain at least two components, antigens that can be recognized by the adaptive immune system (i.e. T and B cells) and an adjuvant that serves as a danger signal to activate the adaptive immune response. Most of us think of vaccines as useful to prevent infections before they occur, like measles and influenza. Indeed, there are now cancer vaccines, such as Gardasil and Cervarix that prevent HPV infections, a leading cause of cervical and head and neck cancers. However, cancer vaccines may also be therapeutic, albeit likely in combination with other approaches that mitigate immune escape. As with any vaccine, there are multiple ways to provide antigen or adjuvant and to administer vaccine. These include not only typical approaches of direct injection of antigen, but also include newer strategies that augment the response to local antigen that is released into the tumor microenvironment under acute inflammatory conditions, including localized radiation and monoclonal antibody therapy (e.g. trastuzumab). Additionally, our understanding of immunologic tolerance is fostering development of designer antigens that eliminate regions recognized by dominant peripheral Treg-mediated tolerance mechanisms.
New approaches that exploit recently defined principles of molecular and cellular immunobiology combined with an expanded ability to monitor the immune response have accelerated clinical application of immunotherapy and vaccines for cancer. Furthermore, the practicing oncology community has begun, in earnest, increasing its focus on ushering immunotherapy into mainstream therapeutics of cancer. Large pharmaceutical companies are rapidly expanding their cancer immunotherapy portfolios by investing in tumor immunotherapy development and acquiring technologies from smaller biotechnology companies. Currently, there are many promising immunotherapies that have or are working their way through clinical trials and FDA registration that could in effect be considered a vaccine or an important component of a vaccine strategy. Prominent examples include new approved treatments that target the CTLA-4 and PD-1 immunologic checkpoints which can be viewed as novel immunologic adjuvants when combined with traditional antigen formulations. Vaccine is the pre-eminent journal for publishing articles related to vaccines and vaccination for infectious disease, cancers and other pathologic conditions. In this first part of a Special Edition of Vaccine focusing on cancer, we are pleased to present a collection of review articles from prominent immunotherapy experts that broadly cover several timely issues related to the ongoing interest of developing cancer vaccines. Keith L. Knutson ∗ Q1 Department of Immunology, Mayo Clinic, Jacksonville, FL, United States Q2 Elizabeth A. Mittendorf Department of Breast Surgical Oncology, MD Anderson Cancer Center, Houston, TX, United States ∗ Corresponding author at: Mayo Clinic Center for Immunology and Immune Therapies, Department of Immunology, Mayo Clinic Florida, Griffin Building, 251B, 4500 San Pablo Rd., Jacksonville, FL 32224, United States. Tel.: +1 904 953 6657. E-mail address: [email protected] (K.L. Knutson)
Available online xxx
http://dx.doi.org/10.1016/j.vaccine.2015.09.086 0264-410X/© 2015 Published by Elsevier Ltd.
Please cite this article in press as: Knutson KL, Mittendorf EA. Cancer vaccines in a new generation of cancer immunotherapy. Vaccine (2015), http://dx.doi.org/10.1016/j.vaccine.2015.09.086
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