Oncolytic viruses

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Oncolytic viruses are viruses that directly or indirectly kill tumor cells . Oncolytic viruses have different mechanisms of action, e.g. B. by infecting and lysing tumor cells , generating an immune response or introducing toxins and tumor suppressor genes into tumor cells. They are used experimentally in the context of oncolytic virotherapy (English: oncolytic cancer virotherapy ) for the treatment of cancer diseases .

properties

An example of a naturally occurring oncolytic virus is the Seneca Valley virus . Most oncolytic viruses are genetically engineered and adapted to their host cells and possibly with toxic , angiogenesis- inhibiting, immunogenic , immunomodulatory or tumor suppressor transgenes .

Oncolytic viruses should reproduce as specifically as possible only in tumor cells and thereby destroy the tumor (oncolysis). The approach is based on the hypothesis that oncolytic viruses specifically infect tumors, at the same time induce a specific immune response and cannot cause any serious side effects. The aim is to achieve a systemic application in which tumor metastases can also be infected throughout the body.

They could also offer a therapeutic alternative for tumors that cannot be surgically removed or that have developed resistance to chemotherapy or radiation therapy. Likewise, synergies could possibly be achieved through the combined treatment with oncolytic viruses and standard treatments such as chemotherapy.

The aims of genetic modification are therefore to improve the specificity , effectiveness or long-term effect, the expression of a transgene or the avoidance of immunosuppression or an overreaction in the immune system .

Adverse effects were among the first oncolytic viruses severe infection patterns with increased morbidity and mortality as well as an immune response against the virus in terms of a vector - immunity which - although asymptomatic - led to a premature degradation of oncolytic viruses before their target cells were achieved.

Currently, different viruses or derived from viral vectors studied in clinical trials, including adenoviruses , herpes simplex virus (oHSV), reovirus , parvovirus B19 , pox viruses , the measles virus , the Sendai virus , the Newcastle disease virus , picornaviruses and Seneca Valley Virus . In contrast to viral vectors for gene therapy or for use as vaccines , however, a multiplication of oncolytic viruses in the host is often desirable ( replication competence ). The replication competence increases the effectiveness of the oncolytic viruses.

history

The connection between a viral infection and tumor regression was described from 1904 onwards, for cervical carcinoma , Burkitt's lymphoma and Hodgkin's lymphoma . From the middle of the 20th century, immunization tests against tumors were also carried out. In the sixties the first successes with polioviruses were achieved on guinea pigs carrying HeLa cells . Also, the adenovirus , Coxsackie virus and several others were investigated. The oncolysis produced was neither complete nor sustained. Due to the lack of success and the lack of genetic engineering methods, virotherapy was largely discontinued in the following years.

Clinical phases

The world's first approved oncolytic virus is Gendicine , which was approved in China in 2003. This was followed by the H101 virus (Oncorine) from Shanghai Sunway Biotech , which was approved in China in 2005. This virus, as well as the similar Onyx-15 virus , has removed viral genes that interact with p53 . These viruses not only infect tumor cells, but preferentially kill tumor cells. While long-term patient survival rates are unknown, the short-term response rate for treatment with H101 and chemotherapy is twice as high as for treatment with chemotherapy alone. The response rate increases when the virus is injected directly into the tumor and the resulting fever is not suppressed.

  • GL ONC1 of Genelux is in Phase I solid tumor.
  • Cavatak is in Phase II for malignant melanoma.

literature

  • Y. Woo: Advances in oncolytic viral therapy. In: Curr Opin Investig Drugs . 7 (6), Jun 2006, pp. 549-559.
  • H. Kasuya: The potential of oncolytic virus therapy for pancreatic cancer. In: Cancer Gene Ther. 12 (9), Sep 2005, pp. 725-736.
  • D. Kirn: Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials. In: Expert Opin Biol Ther. 1 (3), May 2001, pp. 525-538.

Web links

Individual evidence

  1. ^ S. Ayllón Barbellido, J. Campo Trapero, J. Cano Sánchez, MA Perea García, N. Escudero Castaño, A. Bascones Martínez: Gene therapy in the management of oral cancer: Review of the literature . In: Medicina oral, patologia oral y cirugia bucal . tape 13 , no. 1 , 2008, p. E15-E21 , PMID 18167474 ( medicinaoral.com [PDF]).
  2. ↑ a b A. R. Pond, EE Manuelidis: Oncolytic Effect of Poliomyelitis Virus on Human Epidermoid Carcinoma (Hela Tumor) Heterologously Transplanted to Guinea Pigs . In: The American Journal of Pathology . tape 45 , no. 2 , 1964, p. 233-249 , PMID 14202523 , PMC 1907181 (free full text).
  3. ↑ a b c d e f g S. Wennier, S. Li, G. McFadden: Oncolytic virotherapy for pancreatic cancer. In: Expert Rev Mol Med. Volume 13, 2011, p. E18. PMID 21676289 ; PMC 3230120 (free full text).
  4. ↑ a b c M. Ramírez, J. García-Castro, R. Alemany: Oncolytic virotherapy for neuroblastoma. In: Discov Med. Volume 10 (54), 2010, pp. 387-393. PMID 21122470 .
  5. ^ MH Verheije, PJ Rottier: Retargeting of viruses to generate oncolytic agents. In: Adv Virol. 2012, p. 798526. PMID 22312365 ; PMC 3265223 (free full text).
  6. ^ BP Bouchet, C. Caron de Fromentel, A. Puisieux, CM Galmarini: p53 as a target for anti-cancer drug development. In: Crit Rev Oncol Hematol . Volume 58 (3), 2006, pp. 190-207. PMID 16690321 .
  7. ↑ CM Dirven, VW van Beusechem, ML Lamfers, J. Grill, WR Gerritsen, WP Vandertop: Oncolytic adenoviruses for treatment of brain tumors. In: Expert Opin Biol Ther. Volume 2 (8), 2002, pp. 943-952. PMID 12517272 .
  8. ↑ George Dock: The Influence of Complicating Diseases Upon Leukemia. In: The American Journal of the Medical Sciences. Volume 127, Issue 4, 1904, pp. 563-592.
  9. ↑ a b c d e Darshini Kuruppu, Kenneth K. Tanabe: Viral oncolysis by herpes simplex virus and other viruses . In: Cancer Biology and Therapy . tape 4 , no. 5 , 2005, p. 524-531 , doi : 10.4161 / cbt.4.5.1820 .
  10. ^ HA Hoster, RP Zanes, E. Von Haam: Studies in Hodgkin's syndrome; the association of viral hepatitis and Hodgkin's disease; a preliminary report. In: Cancer Research . Volume 9, Number 8, August 1949, pp. 473-480, ISSN  0008-5472 . PMID 18134519 . (PDF)
  11. ^ CM Southam, AE Moore: Clinical studies of viruses as antineoplastic agents with particular reference to Egypt 101 virus. In: Cancer . Volume 5, Number 5, 1952, pp. 1025-1034, ISSN  0008-543X . PMID 12988191 .
  12. ↑ a b M. K. Voroshilova: Potential use of nonpathogenic enteroviruses for control of human disease . In: Progress in medical virology . tape 36 , 1989, pp. 191-202 , PMID 2555836 .
  13. ^ CM Kunin: Cellular Susceptibility To Enteroviruses . In: Bacteriological reviews . tape 28 , no. 4 , 1964, pp. 382-390 , PMID 14244713 , PMC 441234 (free full text).
  14. ↑ E. Kelly, SJ Russell: History of oncolytic viruses: genesis to genetic engineering. In: Molecular therapy: the journal of the American Society of Gene Therapy. Volume 15, Number 4, April 2007, pp. 651-659, ISSN  1525-0016 . doi: 10.1038 / sj.mt.6300108 . PMID 17299401 . nature.com (PDF)
  15. ↑ Sarah E Frew, Stephen M Sammut, Alysha F Shore, Joshua K Ramjist, Sara Al-Bader, Rahim Rezaie, Abdallah S Daar, Peter A Singer: Chinese health biotech and the billion-patient market . In: Nature Biotechnology . tape 26 , no. 1 , 2008, p. 37-53 , doi : 10.1038 / nbt0108-37 , PMID 18183014 .
  16. ↑ a b c d e f K. Garber: China Approves World's First Oncolytic Virus Therapy for Cancer Treatment . In: JNCI Journal of the National Cancer Institute . tape 98 , no. 5 , 2006, p. 298-300 , doi : 10.1093 / jnci / djj111 .
  17. ^ A b c Charlie Schmidt: Amgen spikes interest in live virus vaccines for hard-to-treat cancers . In: Nature Biotechnology . tape 29 , no. 4 , 2011, p. 295-296 , doi : 10.1038 / nbt0411-295 , PMID 21478830 .
  18. ↑ NCT01161498 Study of Safety and Efficacy of OncoVEXGM-CSF With Cisplatin for Treatment of Locally Advanced Head and Neck Cancer ClinicalTrials.gov
  19. ↑ JX-594 ( Memento from December 23, 2010 in the Internet Archive )
  20. ↑ NCT01387555 A Phase 2b Study of Vaccinia Virus to Treat Advanced Liver Cancer (TRAVERSE) ClinicalTrials.gov
  21. ↑ NCT00625456 Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors ClinicalTrials.gov
  22. ↑ CJ Breitbach, SH Thorne, JC Bell, DH Kirn: Targeted and Armed Oncolytic Poxviruses for Cancer: The Lead Example of JX-594 . In: Current Pharmaceutical Biotechnology . 2011, PMID 21740365 .
  23. ↑ Oncolytic viruses mediating anti-tumor immunity in human cancer patients. Oncos Therapeutics, May 19, 2010, accessed March 1, 2017 .
  24. ^ Products. Genelux, accessed March 4, 2012 .
  25. ↑ NCT00794131 Safety Study of GL-ONC1, an Oncolytic Virus, in Patients With Advanced Solid Tumors ClinicalTrials.gov
  26. ↑ Oncolytic activity of Coxsackievirus A21 (CAVATAK ™) in human pancreatic cancer. (June 2011 poster) (PDF; 5.2 MB)
  27. ↑ NCT00832559 A Study of the Intratumoural Administration of CAVATAK to Head and Neck Cancer Patients ClinicalTrials.gov
  28. ↑ NCT01227551 A Study of Intratumoral CAVATAK in Patients With Stage IIIc and Stage IV Malignant Melanoma ClinicalTrials.gov