Autologous tumor cell vaccines for post-operative active-specific immunotherapy of colorectal carcinoma: long-term patient survival and mechanism of function. (2014)

• Record Type: Journal Article
• Authors: Schirrmacher, Volker; Fournier, Philippe; Schlag, Peter
• Is Part Of: Expert review of vaccines. Volume 13:Number 1(2014)
• Page Start: 1
• Page End: 14
• Publication Date: 2014
• Subjects: active-specific immunotherapy -- bone marrow -- cancer stem cell -- dendritic cell -- memory stem cell -- memory T cell -- minimal residual disease -- Newcastle disease virus -- oncolysis -- overall survival -- tumor-associated antigens; Vaccines -- Periodicals; Vaccination -- Periodicals; 615.37205
• DOI: 10.1586/14760584.2014.854169
• Languages: English
• ISSNs: 1476-0584

Abstract

Abstract : Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Surgery remains the primary curative treatment but nearly 50% of patients relapse as consequence of micrometastatic or minimal residual disease (MRD) at the time of surgery. Spontaneous T-cell-mediated immune responses to CRC tumor-associated antigens (TAAs) in tumor-draining lymph nodes and in the bone marrow (BM) lead to infiltration of the tumors by lymphocytes. Certain types of such tumor-infiltrating lymphocytes (TILs) have a positive and others a negative impact on the patients' prognosis. This review focuses on advances in CRC active-specific immunotherapy (ASI), in particular on results from randomized controlled clinical studies employing therapeutic autologous tumor cell vaccines. The observed improvement of long-term survival is explained by activation and mobilization of a pre-existing repertoire of tumor-reactive memory T cells which, according to recent discoveries, reside in distinct niches of patients' bone marrow in neighborhood with hematopoietic (HSC) and mesenchymal (MSC) stem cells. Interestingly, memory T cells also contain a subset of stem memory T cells (SMTs) in addition to effector (EMTs) and central memory T cells (CMTs). The mechanism of function of a therapeutic vaccine in a chronic disease is distinct from that of prophylactic vaccines which have to generate de novo protective immune responses. The advantage of autologous vaccines for mobilization of a broad and highly individual repertoire of memory T cells will be discussed.