SUMMARY / RELATED TOPICS

Tumor antigen vaccine

According to the National Cancer Institute, a tumor antigen vaccine is a "vaccine made of cancer cells, parts of cancer cells, or pure tumor antigens". A tumor antigen vaccine may stimulate the body's immune system to kill cancer cells; as such, tumor antigen vaccines are a type of cancer immunotherapy. Tumor antigen vaccines work the same way that viral vaccines work, by training the immune system to attack cells that contain the antigens in the vaccine; the difference is that the antigens for viral vaccines are derived from viruses or cells infected with virus, while the antigens for tumor antigen vaccines are derived from cancer cells. Since tumor antigens are antigens found in cancer cells but not normal cells, vaccinations containing tumor antigens should train the immune system to target cancer cells not healthy cells. Cancer-specific tumor antigens include peptides from proteins that are not found in normal cells but are activated in cancer cells or peptides containing cancer-specific mutations.

Antigen-presenting cells such as dendritic cells take up antigens from the vaccine, process them into epitopes, present the epitopes to T-cells via Major Histocompatibility Complex proteins. If T-cells recognize the epitope as foreign, the adaptive immune system is activated and target cells that express the antigens. Cancer vaccines can be cell-based, protein- or peptide-based, or gene-based. Cell-based vaccines include tumor cells or tumor cell lysates. Tumor cells from the patient are predicted to contain the greatest spectrum of relevant antigens, but this approach is expensive and requires too many tumor cells from the patient to be effective. Using a combination of established cancer cell lines that resemble the patient’s tumor can overcome these barriers, but this approach has yet to be effective. Canvaxin, which incorporates three melanoma cell lines, failed phase III clinical trials. Another cell-based vaccine strategy involves autologous dendritic cells to which tumor antigens are added.

In this strategy, the antigen-presenting dendritic cells directly stimulate T-cells rather than relying on processing of the antigens by native APCs after the vaccine is delivered. The best known dendritic cell vaccine is Sipuleucel-T; the efficacy of dendritic cell vaccines may be limited due to difficulty in getting the cells to migrate to lymph nodes and interact with T-cells. Peptide-based vaccines consist of cancer specific-epitopes and require an adjuvant to stimulate the immune system and enhance antigenicity. Examples of these epitopes include Her2 peptides, such as NeuVax. However, this approach requires MHC profiling of the patient because of MHC restriction; the need for MHC profile selection can be overcome by using longer peptides or purified protein, which are processed into epitopes by APCs. Gene-based vaccines are composed of the nucleic acid encoding for the gene; the gene is expressed in APCs and the resulting protein product is processed into epitopes. Delivery of the gene is challenging for this type of vaccine.

Viral vaccines work by preventing the spread of the virus. Cancer vaccines can be designed to target common antigens before cancer evolves if an individual has appropriate risk factors. Additional preventive applications include preventing the cancer from evolving further or undergoing metastasis and preventing relapse after remission. Therapeutic vaccines focus on killing existing tumors. While cancer vaccines have been demonstrated to be safe, their efficacy still needs improvement. One way to improve vaccine therapy is by combining the vaccine with other types of immunotherapy aimed at stimulating the immune system. Since tumors evolve mechanisms to suppress the immune system, immune checkpoint blockade has received a lot of attention as a potential treatment to be combined with vaccines. For therapeutic vaccines, combined therapies can be more aggressive, but greater care to ensure the safety of healthy patients is needed for combinations involving preventive vaccines; the clinicaltrials.gov website lists over 1900 trials associated with the term “cancer vaccine”.

Of these, 186 are Phase 3 trials. A recent Trial Watch review of peptide-based vaccines summarized the results of more than 60 trials that were published in the 13 months preceding the article; these trials targeted hematological malignancies, breast cancer and neck cancer, gastroesophageal cancer, lung cancer, pancreatic cancer, prostate cancer, ovarian cancer, colorectal cancers. The antigens included peptides from HER2, telomerase and Wilms’ tumor 1. Several trials used “personalized” mixtures of 12-15 distinct peptides; that is, they contain a mixture of peptides from the patient’s tumor that the patient exhibits an immune response against. The results of these studies indicate that these peptide vaccines have minimal side effects and suggest that they induce targeted immune responses in patients treated with the vaccines; the article discusses 19 clinical trials that were initiated in the same time period. These trials are targeting solid tumors, glioblastoma and breast, ovarian and non-small lung cell cancers and include antigens from MUC1, IDO1, CTAG1B, two VEGF receptors, FLT1 and KDR.

Notably, the IDO1 vaccine is being tested in patients with melanoma in combination with the immune checkpoint inhibitor ipilimumab and the BRAF inhibitor vemurafenib. The following

Pirmin Stekeler-Weithofer

Pirmin Stekeler-Weithofer is a German philosopher and professor of theoretical philosophy at the university of Leipzig. He was the president of the international Ludwig Wittgenstein society and is now a vice-president of this institution; the philosopher studied mathematics and philosophy in Berkeley, Berlin and teaches theoretical philosophy at the university of Leipzig. Stekeler-Weithofer contributes to the philosophy of language, action theory and the relationships between classical and analytical philosophy. An important point is the philosophy of Hegel. Grundprobleme der Logik. Elemente einer Kritik der formalen Vernunft. Berlin 1986, ISBN 3-11-010491-1. Hegels Analytische Philosophie. Die Wissenschaft der Logik als kritische Theorie der Bedeutung. Paderborn 1992, ISBN 3-506-78750-0. Sinn-Kriterien. Die logischen Grundlagen kritischer Philosophie von Platon bis Wittgenstein. Paderborn 1995, ISBN 3-506-78749-7. Was heißt Denken? Von Heidegger über Hölderlin zu Derrida. Bonn University Press, Bonn 2004, ISBN 3-86529-002-7.

Philosophie des Selbstbewußtseins. Hegels System als Formanalyse von Wissen und Autonomie. Suhrkamp, Frankfurt/M. 2005, ISBN 3-518-29349-4. Sprachphilosophie. Probleme und Methoden. Reclam, Stuttgart 2005, ISBN 3-15-018380-4. Philosophiegeschichte. de Gruyter 2006, ISBN 3-11-018556-3 Formen der Anschauung. Eine Philosophie der Mathematik. de Gruyter 2008, ISBN 978-3-11-019435-7. Sinn de Gruyter, Berlin/Boston 2011, ISBN 978-3110254150. Denkströme. Journal der Sächsischen Akademie der Wissenschaften. Im Auftrag der Sächsischen Akademie der Wissenschaften zu Leipzig herausgegeben von Pirmin Stekeler-Weithofer. Leipziger Universitätsverlag, ISSN: 1867-6413. Denken. Wege und Abwege in der Philosophie des Geistes, Mohr Siebeck, Tübingen 2012, ISBN 978-3-16-151935-2. Hegels Phänomenologie des Geistes. Ein dialogischer Kommentar: Band 1: Gewissheit und Vernunft. Band 2: Geist und Religion, Hamburg 2014, ISBN 978-3-7873-2729-4 Manuscript Hegel's Analytic Pragmatism Homepage on University of Leipzig „Die Wahrheit des Bewusstseins ist das Selbstbewusstsein.“ Hegels Weg zur konkreten Selbstbestimmung in der Enzyklopädie