Preferential Autoimmune Response in Prostate Cancer to Cyclin B1 in a Panel of Tumor-Associated Antigens

Dai, Liping; Li, Jitian; Ortega, Rosalia; Qian, Wei; Casiano, Carlos A.; Zhang, Jian Ying

doi:10.1155/2014/827827

Cited by 30 publications

(26 citation statements)

References 45 publications

(59 reference statements)

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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: 84%

“…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. These discrepancies may result either from cancer indications or from a strong variation between individuals, as revealed in Fig.…”

Section: Discussionsupporting

confidence: 66%

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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: 84%

Section: Discussionsupporting

confidence: 66%

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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“…A recent study identified cyclin B1 [36] as an important antibody target in prostate cancer but also in early PSA negative stage of disease [37]. A new study in asymptomatic monoclonal gammopathy (AMG) identified potential targets for prevention of multiple myeloma (MM).…”

Section: Candidate Antigens For Preventative Vaccinesmentioning

confidence: 99%

Cancer immunoprevention

Finn

Beatty

2016

Current Opinion in Immunology

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Cancer immunotherapy is now a reality. The results are phenomenal but the cost is outrageous. Even if the cost eventually comes down and immunotherapy becomes more broadly available, using the knowledge derived from immunotherapy to apply to immunoprevention would be a good strategy. The most likely approach to cancer immunoprevention is cancer vaccines. To date, cancer vaccines have been tested mostly in the setting of advanced disease. Numerous immunosuppressive mechanisms have been identified in the tumor microenvironment as well as systemically that compromise the ability of cancer patients to respond to the vaccines. Multiple approaches are being tested to improve therapeutic cancer vaccine efficacy, including combinations with other immunotherapies. An alternative approach is to administer the vaccines to individuals without cancer but at high risk for cancer. Data in support of this approach and immunoprevention in general is accumulating and clinical testing has started.

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“…Finally, another promising source of vaccine antigens are those targeted by spontaneous anti-tumor immune responses. Two such antigens, Cyclin B1 and SOX2, are found to be common targets of spontaneous immune responses for lung and prostate premalignant lesions and MGUS and MM, respectively (Dai et al, 2014; Kao et al, 2001; Spisek et al, 2007). …”

Section: Prophylactic Cancer Vaccinesmentioning

confidence: 99%

Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines

Lohmueller

Finn

2017

Pharmacology & Therapeutics

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Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated. To this end a multitude of immunotherapies are being tested clinically in new combinations, and many new immunomodulatory antibodies and CARs are in development. A third major immunotherapeutic approach with renewed interest is cancer vaccines. While over 20 years of therapeutic cancer vaccine trials have met with limited success, these studies have laid the groundwork for the use of therapeutic vaccines in combination with other immunotherapies or alone as prophylactic cancer vaccines. Prophylactic vaccines are now poised to revolutionize cancer prevention as they have done for the prevention of infectious diseases. In this review we examine three major cancer immunotherapy modalities: immunomodulatory antibodies, CAR T cell therapy and vaccines. For each we describe the current state of the art and outline major challenges and research directions forward.

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Preferential Autoimmune Response in Prostate Cancer to Cyclin B1 in a Panel of Tumor-Associated Antigens

Cited by 30 publications

References 45 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

Cancer immunoprevention

Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines

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