Cell Based Therapy: Modified Cancer Cells
Colorectal cancer remains a major cause of morbidity and mortality throughout the world, with an incidence that is on the rise. Considering the limitations of surgery and adjuvant chemo and/or radiation therapy in treating CRC patients, a greater emphasis
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Cell Based Therapy: Modified Cancer Cells Vanessa Deschoolmeester, David Kerr, Patrick Pauwels, and Jan B. Vermorken
Introduction The incidence of colorectal cancer (CRC) is on the rise, and patients with recurrent or metastatic colorectal cancer (mCRC) still have a poor long-term survival. Although the development of multi-disciplinary management has improved the survival of CRC, conventional treatments such as chemotherapeutic interventions and radiation therapy only marginally improved longevity [1, 2]. Hence, improved treatment options that selectively target cancer cells and their microenvironment with little or no toxicity to normal tissues are urgently needed [3]. Immunotherapy offers an appealing addition to traditional chemotherapy, with possible long-term protection against tumour recurrences through immunological memory [4]. The requirement for an immune based strategy against cancer is the induction of an effective tumour specific immunity in order to break immunological tolerance to the tumour
V. Deschoolmeester (*) Center for Oncological Research (CORE) Antwerp, University of Antwerp, Antwerp, Belgium Department of Pathology, Antwerp University Hospital, Edegem, Belgium e-mail: [email protected] D. Kerr Nuffield Division of Clinical and Laboratory Sciences, University of Oxford, Oxford, UK P. Pauwels Department of Pathology, Antwerp University Hospital, Edegem, Belgium J.B. Vermorken Center for Oncological Research (CORE) Antwerp, University of Antwerp, Antwerp, Belgium Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium e-mail: [email protected] © Springer International Publishing Switzerland 2017 D. Kerr, R. Johnson (eds.), Immunotherapy for Gastrointestinal Cancer, DOI 10.1007/978-3-319-43063-8_2
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and generate anti-tumour immunity [5]. New insights into the functional dialogue between cancer cells and immune cells and in the hierarchical status of different tumour-immune escape mechanisms at different stages of tumour development have been provided more recently, guiding the design of novel therapeutic strategies [5]. Although immunotherapy in CRC overall has been the subject of several previous reviews [1, 6–10], however this chapter will focus on autologous cell based immunotherapy including adoptive T cell transfer, dendritic cell based vaccines and autologous tumour cell derived vaccines. Also the possibilities of combining immunotherapy with conventional treatment strategies will be briefly touched upon.
Antitumour Immune Response; Key Players As described previously [8], the immune system is capable of promoting an effective immunological reaction to tumour-specific neo-antigens leading to the elimination of cancer cells before clinical expression. However, this immune surveillance period can be followed by a latency period where there is a balance between the immune system and the cancer cells, ultimately tilting towards a phase of immune escape allowing tumour progression and clinical expression. Anti-
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