К ВОПРОСУ О СОЗДАНИИ УНИВЕРСАЛЬНОЙ ИММУНОТЕРАПЕВТИЧЕСКОЙ ПРОТИВОРАКОВОЙ ВАКЦИНЫ

В этом сообщении теоретически обосновывается метод лечения опухолей путем активации in situ дендритных клеток с помощью внутриопухолевой инъекции двух молекулярных «сигналов опасности» бактериального происхождения – плазмидной ДНК, содержащей неметилированные CpG-динуклеотиды, и циклического дигуанозинмонофосфата (цикло-диГМФ). Приведенные в литературе сведения дают основания предположить, что эта процедура способна высвободить из погибающих раковых клеток большое число опухоль-ассоциированных мутантных белков, рекрутировать в ложе опухоли эффекторные иммуноциты, активировать дендритные клетки и в результате – индуцировать мощный системный антираковый Т-клеточный иммунный ответ, способный ликвидировать как первичные солидные опухоли, так и возможные метастазы.

1. Akhmetzhanov, A. R. Dynamics of preventive vs post-diagnostic cancer control using low-impact measures / A. R. Akhmetzhanov, M. E. Hochberg // eLife. ‒ 2015. ‒ Vol. 4. ‒ Art. e06266. https://doi.org/10.7554/eLife.06266

2. Welch, H. G. Overdiagnosis in cancer / H. G. Welch, W. C. Black // J. of the Nat. Cancer Inst. ‒ 2010. ‒ Vol. 102, N 9. ‒ P. 605‒613. https://doi.org/10.1093/jnci/djq099

3. Combining radiotherapy with immunotherapy: the past, the present and the future / E. J. van Limbergen [et al.] // Brit. J. of Radiology. ‒ 2017. ‒ Vol. 90, N 1076. ‒ Art. 20170157. https://doi.org/10.1259/bjr

4. Core needle biopsy of breast cancer tumors increases distant metastases in a mouse model / E. G. Mathenge [et al.] // Neoplasia. ‒ 2014. ‒ Vol. 16, N 11. ‒ P. 950–960. https://doi.org/10.1016/j.neo.2014.09.004

5. Therapy’s shadow: a short history of the study of resistance to cancer chemotherapy / P. Keating [et al.] // Frontiers in Pharmacology. ‒ 2013. ‒ Vol. 4. ‒ Art. 58. https://doi.org/10.3389/fphar.2013.00058

6. Cancer stem cell plasticity drives therapeutic resistance / M. R. Doherty [et al.] // Cancers. ‒ 2016. ‒ Vol. 8. ‒ Art. 8. https://doi.org/10.3390/cancers8010008

7. Second cancer after radiotherapy, 1981–2007 / D. Bartkowiak [et al.] // Radiotherapy and Oncology. ‒ 2012. ‒ Vol. 105, N 1. ‒ P. 122–126. https://doi.org/10.1016/j.radonc.2011.09.013

8. Sverdlov, E. D. Multidimensional complexity of cancer. Simple solutions are needed / E. D. Sverdlov // Biochemistry. ‒ 2016. ‒ Vol. 81, N 7. ‒ P. 731–738. https://doi.org/10.1134/S0006297916070099

9. Folkman, J. Cancer without disease / J. Folkman, R. Kalluri // Nature. ‒ 2004. ‒ Vol. 427, N 6977. ‒ P. 787. https://doi. org/10.1038/427787a

10. Cancer mortality among recipients of solid-organ transplantation in Ontario, Canada / S. A. Acuna [et al.] // JAMA Oncology. ‒ 2016. ‒ Vol. 2, N 4. ‒ P. 463‒469. https://doi.org/10.1001/jamaoncol.2015.5137

11. Itoh, K. Interleukin 2 activation of cytotoxic T-lymphocytes infiltrating into human metastatic melanomas / K. Itoh, A. B. Tilden, C. M. Balch // Cancer Res. ‒ 1986. ‒ Vol. 46, N 6. ‒ P. 3011–3017.

12. Ohta, A. A metabolic immune checkpoint: adenosine in tumor microenvironment / A. Ohta // Frontiers in Immunology. ‒ 2016. ‒ Vol. 7. ‒ Art. 109. https://doi.org/10.3389/fimmu.2016.00109

13. Kumar, T. Spontaneous regression of thoracic malignancies / T. Kumar, N. Patel, A. Talwar // Respiratory Medicine. ‒ 2010. ‒ Vol. 104, N 10. ‒ P. 1543–1550. https://doi.org/10.1016/j.rmed.2010.04.026

14. Jackson, R. Saint Peregrine, O. S. M. – the patron saint of cancer patients / R. Jackson // Canad. Med. Assoc. J. ‒ 1974. ‒ Vol. 111, N 8. ‒ P. 824–827.

15. Kienle, G. S. Fever in cancer treatment: Coley’s therapy and epidemiologic observations / G. S. Kienle // Global Advances in Health and Medicine. ‒ 2012. ‒ Vol. 1, N 1. ‒ P. 92–100. https://doi.org/10.7453/gahmj.2012.1.1.016

16. Krone, B. The biography of the immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies / B. Krone, K. F. Kolmel, J. M. Grange // BMC Cancer. ‒ 2014. ‒ Vol. 14, N 1. ‒ Art. 595. https://doi. org/10.1186/1471-2407-14-595

17. Haro, A. S. The effect of BCG-vaccination and tuberculosis on the risk of leukaemia / A. S. Haro // Developments in Biological Standardization. ‒ 1986. ‒ Vol. 58, pt. A. ‒ P. 433–439.

18. Tsung, K. Lessons from Coley’s toxin / K. Tsung, J. A. Norton // Surgical Oncology. ‒ 2006. ‒ Vol. 15, N 1. ‒ P. 25–28. https://doi.org/10.1016/j.suronc.2006.05.002

19. Garg, A. D. Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses / A. D. Garg, P. Agostinis // Immunological Rev. ‒ 2017. ‒ Vol. 280, N 1. ‒ P. 126–148. https://doi.org/10.1111/imr.12574

20. Trial watch: immunogenic cell death induction by anticancer chemotherapeutics / A. Garg [et al.] // Oncoimmunology. ‒ 2017. ‒ Vol. 6, N 12. ‒ Art. e1386829. https://doi.org/10.1080/2162402X.2017.1386829

21. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines / L. Vandenberk [et al.] // Frontiers in Immunology. ‒ 2016. ‒ Vol. 6. ‒ Art. 663. https://doi.org/10.3389/fimmu.2015.00663

22. Posey, A. D. Cancer killers / A. D. Posey, C. H. June, B. L. Levine // Scientific Amer. ‒ 2017. ‒ Vol. 316, N 3. ‒ P. 38–43. https://doi.org/10.1038/scientificamerican0317-38

23. Hammerich, L. In situ vaccination: cancer immunotherapy both personalized and off-the-shelf / L. Hammerich, A. Binder, J. D. Brody // Molecular Oncology. ‒ 2015. ‒ Vol. 9, N 10. ‒ P. 1966–1981. https://doi.org/10.1016/j.molonc.2015.10.016

24. Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma / N. Klein-González [et al.] // Expert Rev. Vaccines. ‒ 2011. ‒ Vol. 10, N 3. ‒ P. 295‒298. https://doi.org/10.1586/erv.11.6

25. Therapeutic injection of a C-type CpG ODN induced an antitumor immune response in C57/BL6 mice of orthotopically transplanted hepatocellular carcinoma / H. Jia [et al.] // Oncology Res. ‒ 2016. ‒ Vol. 23, N 6. ‒ P. 321–326. https://doi. org/10.3727/096504016X14570992647041

26. STING is a direct innate immune sensor of cyclic di-GMP / D. L. Burdette [et al.] // Nature. ‒ 2011. ‒ Vol. 478, N 7370. ‒ P. 515–518. https://doi.org/10.1038/nature10429

27. STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer / D. Chandra [et al.] // Cancer Immunology Res. ‒ 2014. ‒ Vol. 2, N 9. ‒ P. 901–910. https://doi.org/10.1158/2326-6066.CIR-13-0123

28. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity / L. Corrales [et al.] // Cell Reports. ‒ 2015. ‒ Vol. 11, N 7. ‒ P. 1018–1030. https://doi.org/ 10.1016/j.celrep.2015.04.031

29. Rivera Vargas, T. Rationale for stimulator of interferon genes-targeted cancer immunotherapy / T. Rivera Vargas, I. Benoit-Lizon, L. Apetoh // European J. of Cancer. ‒ 2017. ‒ Vol. 75. ‒ P. 86–97. https://doi.org/10.1016/j.ejca.2016.12.028

30. Carpentier, A. F. CpG-oligonucleotides for cancer immunotherapy: review of the literature and potential applications in malignant glioma / A. F. Carpentier, G. Auf, J. Y. Delattre // Frontiers in Bioscience. ‒ 2003. ‒ Vol. 8, N 5. ‒ P. 115–127. https://doi.org/10.2741/934

31. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study / J. D. Brody [et al.] // J. of Clinical Oncology. ‒ 2010. ‒ Vol. 28, N 28. ‒ P. 4324‒4332. https://doi.org/10.1200/JCO.2010.28.9793

32. Simultaneous delivery of doxorubicin and immunostimulatory CpG motif to tumors using a plasmid DNA/doxorubicin complex in mice / Y. Mizuno [et al.] // J. of Controlled Release. ‒ 2010. ‒ Vol. 141, N 2. ‒ P. 252–259. https://doi. org/10.1016/j.jconrel.2009.09.014

33. Promising targets for cancer immunotherapy: TLRs, RLRs, and STING-mediated innate immune pathways / K. Li [et al.] // Intern. J. of Molecular Sciences. ‒ 2017. ‒ Vol. 18, N 2. ‒ Art. 404. https://doi.org/10.3390/ijms18020404

34. Zinchenko, A. I. Construction of plasmid enriched with immunostimulatory CpG motifs / A. I. Zinchenko, S. V. Kvach, A. S. Shchokolova // Eastern European Scientific J. ‒ 2014. – N 3. ‒ P. 10–13. https://doi.org/10.12851/EESJ201406C01ART02

35. Enzymatic synthesis of c-di-GMP using inclusion bodies of Thermotoga maritima full-length diguanylatecyclase / A. S. Korovashkina [et al.] // J. Biotechnol. ‒ 2012. ‒ Vol. 164, N 2. ‒ P. 276–280. https://doi.org/10.1016/j.jbiotec.2012.12.006

36. McNeel, D. G. Therapeutic cancer vaccines: how much closer are we? / D. G. McNeel // BioDrugs. ‒ 2017. ‒ Vol. 32, N 1. ‒ P. 1‒7. https://doi.org/10.1007/s40259-017-0257-y

37. Cancer immunogenomics: computational neoantigen identification and vaccine design / J. Hundal [et al.] // Cold Spring Harbor Symposia on Quantitative Biology. ‒ 2017. ‒ Vol. 81. ‒ P. 105‒111. https://doi.org/10.1101/sqb.2016.81.030726