Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

Andersen, Rikke; Sørensen, Rikke Bæk; Ritter, Cathrin; Svane, Inge Marie; Becker, Jürgen C.; Straten, Per thor; Andersen, Mads Hald

doi:10.1007/s00262-010-0933-y

Cited by 8 publications

(11 citation statements)

References 29 publications

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“…We also confirmed the spontaneous CCNB1-specific IgG response observed in healthy and cancer patients (30,31,(53)(54)(55)). We observed a similar level of anti-CCNB1 Abs in patients and healthy donors (31).…”

Section: Discussionsupporting

confidence: 72%

“…We observed a similar level of anti-CCNB1 Abs in patients and healthy donors (31). This is at variance with other studies in which the level was either higher (53,54) or lower (55) in cancer patients than in healthy donors.…”

Section: Discussioncontrasting

confidence: 56%

“…Tumor-specific CTL response raised against CCNB1 has already been observed in healthy donors and cancer patients (27)(28)(29), whereas the CD4 response specific to CCNB1 has scarcely been investigated and only in healthy donors (30). Strikingly, it has also been observed that CCNB1-specific Abs pre-exist in healthy donors (30,31). Because CCNB1 is widely expressed in malignancies and is not dispensable for tumor cells, we evaluated a part of its vaccine potential by performing a comprehensive analysis of the CD4 T cell response specific to CCNB1 in healthy and cancer patients.…”

mentioning

confidence: 97%

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The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Chevaleyre

Benhamouda

Favry

et al. 2015

The Journal of Immunology

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Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines.

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Section: Discussionsupporting

confidence: 72%

Section: Discussioncontrasting

confidence: 56%

mentioning

confidence: 97%

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The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Chevaleyre

Benhamouda

Favry

et al. 2015

The Journal of Immunology

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“…Other studies supporting similar mechanisms relate to the role of immunity against cyclin B1, previously identified by us [35,36] and others [37*][38] as a tumor antigen. In healthy cells, cyclin B1 serves as a cell cycle regulatory molecule expressed in small amounts in the nucleus of dividing cells as they transition from G2 to M phase of the cell cycle.…”

Section: Childhood Illnesses and Cancer Immunosurveillancesupporting

confidence: 75%

Epidemiologic perspective on immune-surveillance in cancer

Cramer¹,

Finn²

2011

Current Opinion in Immunology

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Common “themes” in epidemiology related to cancer risk beg a comprehensive mechanistic explanation. As people age, risk for cancer increases. Obesity and smoking increase the risk for many types of cancer. History of febrile childhood diseases lowers the risk for melanomas, leukemias, non-Hodgkin’s lymphoma (NHL) and ovarian cancer. Increasing number of ovulatory cycles uninterrupted by pregnancies correlate positively with breast, endometrial and ovarian cancer risk while pregnancies and breastfeeding lower the risk for these cancers as well as cancers of the colon, lung, pancreas and NHL. Chronic inflammatory events such endometriosis or mucosal exposure to talc increase the risk for several types of cancer. Mechanisms so far considered are site specific and do not explain multiple associations. We propose that most of these events affect cancer immunosurveillance by changing the balance between an effective immune response and immune tolerance of an emerging cancer. We review recently published data that suggest that immune mechanisms underlie most of the observed epidemiologic associations with cancer risk.

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“…Many healthy individuals have cyclin B1-specific memory T cells and antibodies (42,43). In a spontaneous mouse tumor model, cyclin B1 vaccine prevents cancer occurrence (44).…”

Section: Support For Prophylactic Cancer Vaccines From the Crossroadsmentioning

confidence: 99%

Vaccines for Cancer Prevention: A Practical and Feasible Approach to the Cancer Epidemic

Finn

2014

Cancer Immunology Research

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Concerted efforts of tumor immunologists over more than two decades contributed numerous well-defined tumor antigens, many of which were promptly developed into cancer vaccines and tested in animal models and in clinical trials. Encouraging results from animal models were seldom recapitulated in clinical trials. The impediment to greater success of these vaccines has been their exclusive use for cancer therapy. What clinical trials primarily revealed were the numerous ways in which cancer and/or standard treatments for cancer could suppress the patient’s immune system making it very difficult to elicit effective immunity with therapeutic vaccines. In contrast, there is an extensive database of information from experiments in appropriate animal models showing that prophylactic vaccination is highly effective and safe. There are also studies that show that healthy people have immune responses against antigens expressed on tumors, some generated in response to viral infections and others in response to various non-malignant acute inflammatory events. These immune responses do not appear dangerous and do not cause autoimmunity. Epidemiology studies have shown that these immune responses may reduce cancer risk significantly. Vaccines based on tumor antigens that are expressed differentially between tumors and normal cells and can stimulate immunity, and whose safety and efficacy have been proven in animal models and to the extent possible in therapeutic clinical trials, should be considered prime candidates for prophylactic cancer vaccines.

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Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

Cited by 8 publications

References 29 publications

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Epidemiologic perspective on immune-surveillance in cancer

Vaccines for Cancer Prevention: A Practical and Feasible Approach to the Cancer Epidemic

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