The promising alliance of anti-cancer electrochemotherapy with immunotherapy

Cancer and Metastasis Reviews

Volumn 35, Issue 2, 2016, Pages 165-177

  Calvet, Christophe Y ^a   Mir, Lluis M ^a  

^a CNRS   (France)

Author keywords

Cancer; Electrochemotherapy; Electrogenetherapy; Immunity; Immunotherapy; Metastasis

Indexed keywords

ANTINEOPLASTIC AGENT; BLEOMYCIN; CISPLATIN; CYTOKINE; IMMUNOSTIMULATING AGENT; NAKED DNA; VIRUS VECTOR; CANCER VACCINE; DNA VACCINE; IMMUNOLOGIC FACTOR;

CANCER ADJUVANT THERAPY; CANCER CELL; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER THERAPY; CELL DEATH; CELL FUNCTION; CLINICAL EFFECTIVENESS; CLINICAL EVALUATION; CLINICAL PROTOCOL; CLINICAL TRIAL (TOPIC); CYTOTOXICITY; DNA IMMUNIZATION; DRUG EFFICACY; DRUG MECHANISM; ELECTROCHEMOTHERAPY; ELECTROGENETHERAPY; ELECTROPORATION; GENETIC TOXICOLOGY; GENETIC TRANSFECTION; HUMAN; LOCAL THERAPY; NONHUMAN; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; THERAPY EFFECT; TREATMENT CONTRAINDICATION; TREATMENT PLANNING; TREATMENT RESPONSE; TUMOR REGRESSION; ANIMAL; DRUG DELIVERY SYSTEM; GENE THERAPY; GENE TRANSFER; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; MULTIMODALITY CANCER THERAPY; NEOPLASMS; PATHOLOGY; PROCEDURES; TRANSLATIONAL RESEARCH;

ANIMALS; ANTINEOPLASTIC AGENTS; CANCER VACCINES; COMBINED MODALITY THERAPY; CYTOKINES; DRUG DELIVERY SYSTEMS; ELECTROCHEMOTHERAPY; ELECTROPORATION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOTHERAPY; NEOPLASMS; TRANSLATIONAL MEDICAL RESEARCH; VACCINES, DNA;

EID: 84975860048     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-016-9615-3     Document Type: Review

References (85)

1. Escoffre, J. M., Portet, T., Wasungu, L., Teissie, J., Dean, D., & Rols, M. P. (2009). What is (still not) known of the mechanism by which electroporation mediates gene transfer and expression in cells and tissues. Molecular Biotechnology, 41(3), 286-295. doi: 10. 1007/s12033-008-9121-0.
2. Breton, M., & Mir, L. M. (2011). Microsecond and nanosecond electric pulses in cancer treatments. Bioelectromagnetics. doi: 10. 1002/bem. 20692.
3. Sale, A. J., & Hamilton, W. A. (1968). Effects of high electric fields on micro-organisms. 3. Lysis of erythrocytes and protoplasts. Biochimica et Biophysica Acta, 163(1), 37-43.
4. Neumann, E., Schaefer-Ridder, M., Wang, Y., & Hofschneider, P. H. (1982). Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO Journal, 1(7), 841-845.
5. Mir, L. M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek, J., Jr., et al. (1991). Electrochemotherapy, a new antitumor treatment: first clinical trial. Comptes Rendus de l'Academie des Sciences. Serie III, 313(13), 613-618.
6. Belehradek, M., Domenge, C., Luboinski, B., Orlowski, S., Belehradek, J., Jr., & Mir, L. M. (1993). Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer, 72(12), 3694-3700.
7. Villemejane, J., & Mir, L. M. (2009). Physical methods of nucleic acid transfer: general concepts and applications. British Journal of Pharmacology, 157(2), 207-219. doi: 10. 1111/j. 1476-5381. 2009. 00032. x.
8. Nayerossadat, N., Maedeh, T., & Ali, P. A. (2012). Viral and nonviral delivery systems for gene delivery. Advanced Biomedical Research, 1, 27. doi: 10. 4103/2277-9175. 98152.
9. Mir, L. M. (2006). Bases and rationale of the electrochemotherapy. EJC Supplements, 4(11), 38-44. doi: 10. 1016/j. ejcsup. 2006. 08. 005.
10. Escoffre, J. M., & Rols, M. P. (2012). Electrochemotherapy: progress and prospects. Current Pharmaceutical Design, 18(23), 3406-3415.
11. Mir, L. M., Banoun, H., & Paoletti, C. (1988). Introduction of definite amounts of nonpermeant molecules into living cells after electropermeabilization-direct access to the cytosol. Experimental Cell Research, 175(1), 15-25. doi: 10. 1016/0014-4827(88)90251-0.
12. Pron, G., Belehradek, J., Jr., & Mir, L. M. (1993). Identification of a plasma membrane protein that specifically binds bleomycin. Biochemical and Biophysical Research Communications, 194(1), 333-337. doi: 10. 1006/bbrc. 1993. 1824.
13. Cemazar, M., Sersa, G., & Miklavcic, D. (1998). Electrochemotherapy with cisplatin in the treatment of tumor cells resistant to cisplatin. Anticancer Research, 18(6A), 4463-4466.
14. Poddevin, B., Orlowski, S., Belehradek, J., Jr., & Mir, L. M. (1991). Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture. Biochemical Pharmacology, 42(Suppl), S67-75.
15. Tounekti, O., Pron, G., Belehradek, J., & Mir, L. M. (1993). Bleomycin, an apoptosis-mimetic drug that induces 2 types of cell-death depending on the number of molecules internalized. Cancer Res, 53(22), 5462-5469.
16. Frandsen, S. K., Gibot, L., Madi, M., Gehl, J., & Rols, M. P. (2015). Calcium electroporation: evidence for differential effects in normal and malignant cell lines, evaluated in a 3D spheroid model. PLoS One, 10(12), e0144028. doi: 10. 1371/journal. pone. 0144028.
17. Frandsen, S. K., Gissel, H., Hojman, P., Tramm, T., Eriksen, J., & Gehl, J. (2012). Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res, 72(6), 1336-1341. doi: 10. 1158/0008-5472. CAN-11-3782.
18. Tafuto, S., von Arx, C., De Divitiis, C., Maura, C. T., Palaia, R., Albino, V., et al. (2015). Electrochemotherapy as a new approach on pancreatic cancer and on liver metastases. International Journal of Surgery, 21(Suppl 1), S78-82. doi: 10. 1016/j. ijsu. 2015. 04. 095.
19. Cabula, C., Campana, L. G., Grilz, G., Galuppo, S., Bussone, R., De Meo, L., et al. (2015). Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis. Annals of Surgical Oncology, 22(Suppl 3), 442-450. doi: 10. 1245/s10434-015-4779-6.
20. Jarm, T., Cemazar, M., Miklavcic, D., & Sersa, G. (2010). Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert Review on Anticancer Therapy, 10(5), 729-746. doi: 10. 1586/era. 10. 43.
21. Marty, M., Sersa, G., Garbay, J. R., Gehl, J., Collins, C. G., Snoj, M., et al. (2006). Electrochemotherapy-an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Supplements, 4(11), 3-13. doi: 10. 1016/j. ejcsup. 2006. 08. 002.
22. Mir, L. M., Gehl, J., Sersa, G., Collins, C. G., Garbay, J. R., Billard, V., et al. (2006). Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator (TM) by means of invasive or noninvasive electrodes. EJC Supplements, 4(11), 14-25. doi: 10. 1016/j. ejcsup. 2006. 08. 003.
23. Miklavcic, D., Mali, B., Kos, B., Heller, R., & Sersa, G. (2014). Electrochemotherapy: from the drawing board into medical practice. Biomedical Engineering Online, 13(1), 29. doi: 10. 1186/1475-925X-13-29.
24. Quaglino, P., Mortera, C., Osella-Abate, S., Barberis, M., Illengo, M., Rissone, M., et al. (2008). Electrochemotherapy with intravenous bleomycin in the local treatment of skinmelanomametastases. Annals of Surgical Oncology, 15(8), 2215-2222. doi: 10. 1245/ s10434-008-9976-0.
25. Gaudy, C., Richard, M. A., Folchetti, G., Bonerandi, J. J., & Grob, J. J. (2006). Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma. Journal of Cutaneous Medicine and Surgery, 10(3), 115-121. doi: 10. 2310/ 7750. 2006. 00037.
26. Caraco, C., Mozzillo, N., Marone, U., Simeone, E., Benedetto, L., Di Monta, G., et al. (2013). Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis. Bmc Cancer, 13, Doi 10. 1186/1471-2407-13-564.
27. Snoj, M., Rudolf, Z., Paulin-Kosir, S. M., Cemazar, M., Snoj, R., & Sersa, G. (2006). Long lasting complete response in melanoma treated by electrochemotherapy. EJC Supplements, 4(11), 26-28. doi: 10. 1016/j. ejcsup. 2006. 08. 004.
28. Colombo, G. L., Matteo, S. D., & Mir, L. M. (2008). Costeffectiveness analysis of electrochemotherapy with the Cliniporatortrade mark vs other methods for the control and treatment of cutaneous and subcutaneous tumors. Therapeutics and Clinical Risk Management, 4(2), 541-548.
29. Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., et al. (1990). Direct gene transfer into mouse muscle in vivo. Science, 247(4949 Pt 1), 1465-1468.
30. Andre, F. M., Cournil-Henrionnet, C., Vernerey, D., Opolon, P., & Mir, L. M. (2006). Variability of naked DNA expression after direct local injection: the influence of the injection speed. Gene Therapy, 13(23), 1619-1627. doi: 10. 1038/sj. gt. 3302827.
31. Dolter, K. E., Evans, C. F., Ellefsen, B., Song, J., Boente-Carrera, M., Vittorino, R., et al. (2011). Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine, 29(4), 795-803. doi: 10. 1016/j. vaccine. 2010. 11. 011.
32. Chernajovsky, Y., Gould, D. J., & Podhajcer, O. L. (2004). Gene therapy for autoimmune diseases: quo vadis? Nature Reviews Immunology, 4(10), 800-811. doi: 10. 1038/nri1459.
33. Mir, L. M. (2009). Nucleic acids electrotransfer-based gene therapy (electrogenetherapy): past, current, and future. Molecular Biotechnology, 43(2), 167-176. doi: 10. 1007/s12033-009-9192-6.
34. Satkauskas, S., Bureau, M. F., Puc, M., Mahfoudi, A., Scherman, D., Miklavcic, D., et al. (2002). Mechanisms of in vivo DNA electrotransfer: respective contributions of cell electropermeabilization and DNA electrophoresis. Molecular Therapeutics, 5(2), 133-140. doi: 10. 1006/mthe. 2002. 0526.
35. Andre, F. M., Gehl, J., Sersa, G., Preat, V., Hojman, P., Eriksen, J., et al. (2008). Efficiency of high-and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Human Gene Therapy, 19(11), 1261-1271. doi: 10. 1089/hgt. 2008. 060.
36. Gothelf, A., & Gehl, J. (2010). Gene electrotransfer to skin; review of existing literature and clinical perspectives. Current Gene Therapy, 10(4), 287-299.
37. Andre, F. M., & Mir, L. M. (2010). Nucleic acids electrotransfer in vivo: mechanisms and practical aspects. Current Gene Therapy, 10(4), 267-280.
38. Combadiere, B., & Liard, C. (2011). Review of transcutaneous and intradermal vaccination. Human Vaccine, 7(8), 811-827. doi: 10. 4161/Hv. 7. 8. 16274.
39. Lambricht, L., Lopes, A., Kos, S., Sersa, G., Preat, V., & Vandermeulen, G. (2015). Clinical potential of electroporation for gene therapy and DNA vaccine delivery. Expert Opinion Drug Delivery. doi: 10. 1517/17425247. 2016. 1121990.
40. Kutzler, M. A., & Weiner, D. B. (2008). DNA vaccines: ready for prime time? Nature Reviews Genetics, 9(10), 776-788. doi: 10. 1038/nrg2432.
41. Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011). Natural innate and adaptive immunity to cancer. Annual Review of Immunology, 29, 235-271. doi: 10. 1146/annurevimmunol-031210-101324.
42. Braumuller, H., Wieder, T., Brenner, E., Assmann, S., Hahn, M., Alkhaled, M., et al. (2013). T-helper-1-cell cytokines drive cancer into senescence. Nature, 494(7437), 361-365. doi: 10. 1038/ nature11824.
43. Liu, M. A., & Ulmer, J. B. (2005). Human clinical trials of plasmid DNA vaccines. Advances in Genetics, 55, 25-40. doi: 10. 1016/ S0065-2660(05)55002-8.
44. Gothelf, A., & Gehl, J. (2012). What you always needed to know about electroporation based DNA vaccines. Human Vaccine Immunotherapy, 8(11), 1694-1702. doi: 10. 4161/hv. 22062.
45. Aurisicchio, L., Mancini, R., & Ciliberto, G. (2013). Cancer vaccination by electro-gene-transfer. Expert Review Vaccines, 12(10), 1127-1137. doi: 10. 1586/14760584. 2013. 836903.
46. Roos, A. K., Moreno, S., Leder, C., Pavlenko, M., King, A., & Pisa, P. (2006). Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Molecular Therapy, 13(2), 320-327. doi: 10. 1016/j. ymthe. 2005. 08. 005.
47. Colombo, M. P., & Trinchieri, G. (2002). Interleukin-12 in antitumor immunity and immunotherapy. Cytokine Growth Factor Review, 13(2), 155-168.
48. Yamashita, Y., Shimada, M., Hasegawa, H., Minagawa, R., Rikimaru, T., Hamatsu, T., et al. (2001). Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res, 61(3), 1005-1012.
49. Kishida, T., Asada, H., Satoh, E., Tanaka, S., Shinya, M., Hirai, H., et al. (2001). In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice. Gene Therapy, 8(16), 1234-1240. doi: 10. 1038/sj. gt. 3301519.
50. Lohr, F., Lo, D. Y., Zaharoff, D. A., Hu, K., Zhang, X. W., Li, Y. P., et al. (2001). Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation. Cancer Research, 61(8), 3281-3284.
51. Heller, L., Merkler, K., Westover, J., Cruz, Y., Coppola, D., Benson, K., et al. (2006). Evaluation of toxicity following electrically mediated interleukin-12 gene delivery in a B16mousemelanomamodel. Clinical Cancer Research, 12(10), 3177-3183. doi: 10. 1158/1078-0432. Ccr-05-2727.
52. Cemazar, M., Jarm, T., & Sersa, G. (2010). Cancer electrogene therapy with interleukin-12. Current Gene Therapy, 10(4), 300-311.
53. Daud, A. I., DeConti, R. C., Andrews, S., Urbas, P., Riker, A. I., Sondak, V. K., et al. (2008). Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. Journal of Clinical Oncology, 26(36), 5896-5903. doi: 10. 1200/JCO. 2007. 15. 6794.
54. Mir, L. M., Orlowski, S., Poddevin, B., & Belehradek, J., Jr. (1992). Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of the host's defenses. European Cytokine Network, 3(3), 331-334.
55. Sersa, G., Miklavcic, D., Cemazar, M., Belehradek, J., Jarm, T., & Mir, L. M. (1997). Electrochemotherapy with CDDP on LPB sarcoma: comparison of the anti-tumor effectiveness in immunocompetent and immunodeficient mice. Bioelectrochemistry and Bioenergetics, 43(2), 279-283. doi: 10. 1016/S0302-4598(96)05194-X.
56. Mir, L. M., Orlowski, S., Belehradek, J., Jr., & Paoletti, C. (1991). Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. European Journal of Cancer, 27(1), 68-72.
57. Gerlini, G., Sestini, S., Di Gennaro, P., Urso, C., Pimpinelli, N., & Borgognoni, L. (2013). Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy. Clinical and Experimental Metastasis, 30(1), 37-45. doi: 10. 1007/s10585-012-9505-1.
58. Roux, S., Bernat, C., Al-Sakere, B., Ghiringhelli, F., Opolon, P., Carpentier, A. F., et al. (2008). Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. Cancer Immunology Immunotherapy, 57(9), 1291-1300. doi: 10. 1007/s00262-008-0462-0.
59. Mekid, H., Tounekti, O., Spatz, A., Cemazar, M., El Kebir, F. Z., & Mir, L. M. (2003). In vivo evolution of tumour cells after the generation of double-strand DNA breaks. British Journal of Cancer, 88(11), 1763-1771. doi: 10. 1038/sj. bjc. 6600959.
60. Sersa, G., Kotnik, V., Cemazar, M., Miklavcic, D., & Kotnik, A. (1996). Electrochemotherapy with bleomycin in SA-1 tumor-bearing mice-natural resistance and immune responsiveness. Anticancer Drugs, 7(7), 785-791.
61. Calvet, C. Y., Famin, D., Andre, F. M., & Mir, L. M. (2014). Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Oncoimmunology, 3, e28131. doi: 10. 4161/onci. 28131.
62. Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L. (2013). Immunogenic cell death in cancer therapy. Annual Reviews Immunology, 31, 51-72. doi: 10. 1146/annurev-immunol-032712-100008.
63. Calvet, C. Y., Andre, F. M., & Mir, L. M. (2014). The culture of cancer cell lines as tumorspheres does not systematically result in cancer stem cell enrichment. PLoS One, 9(2), e89644. doi: 10. 1371/ journal. pone. 0089644.
64. Ledur, P. F., Villodre, E. S., Paulus, R., Cruz, L. A., Flores, D. G., & Lenz, G. (2012). Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells. Purinergic Signal, 8(1), 39-48. doi: 10. 1007/s11302-011-9252-9.
65. Inoda, S., Hirohashi, Y., Torigoe, T., Morita, R., Takahashi, A., Asanuma, H., et al. (2011). Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells. American Journal of Pathology, 178(4), 1805-1813. doi: 10. 1016/j. ajpath. 2011. 01. 004.
66. Calvet, C. Y., Andre, F. M., & Mir, L. M. (2014). Dual therapeutic benefit of electroporation-mediated DNA vaccination in vivo: enhanced gene transfer and adjuvant activity. Oncoimmunology, 3, e28540. doi: 10. 4161/onci. 28540.
67. Liu, J., Kjeken, R., Mathiesen, I., & Barouch, D. H. (2008). Recruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation. Journal of Virology, 82(11), 5643-5649. doi: 10. 1128/JVI. 02564-07.
68. Babiuk, S., Baca-Estrada, M. E., Foldvari, M., Middleton, D. M., Rabussay, D., Widera, G., et al. (2004). Increased gene expression and inflammatory cell infiltration caused by electroporation are both important for improving the efficacy of DNA vaccines. Journal of Biotechnology, 110(1), 1-10. doi: 10. 1016/j. jbiotec. 2004. 01. 015.
69. Mir, L. M., Roth, C., Orlowski, S., Quintin-Colonna, F., Fradelizi, D., Belehradek, J., Jr., et al. (1995). Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2. Journal of Immunotherapy with Emphasis on Tumor Immunology, 17(1), 30-38.
70. Orlowski, S., An, D., Belehradek, J., Jr., & Mir, L. M. (1998). Antimetastatic effects of electrochemotherapy and of histoincompatible interleukin-2-secreting cells in the murine Lewis lung tumor. Anticancer Drugs, 9(6), 551-556.
71. Ramirez, L. H., Orlowski, S., An, D., Bindoula, G., Dzodic, R., Ardouin, P., et al. (1998). Electrochemotherapy on liver tumours in rabbits. British Journal of Cancer, 77(12), 2104-2111.
72. Heller, L., Pottinger, C., Jaroszeski, M. J., Gilbert, R., & Heller, R. (2000). In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity. Melanoma Research, 10(6), 577-583. doi: 10. 1097/00008390-200012000-00010.
73. Andersen, M. H., Gehl, J., Reker, S., Pedersen, L. O., Becker, J. C., Geertsen, P., et al. (2003). Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration. Seminars in Cancer Biology, 13(6), 449-459. doi: 10. 1016/j. semcancer. 2003. 09. 009.
74. Sersa, G., Cemazar, M., Menart, V., Gaberc Porekar, V., & Miklavcic, D. (1997). Anti-tumor effectiveness of electrochemotherapy with bleomycin is increased by TNF-alpha on SA-1 tumors in mice. Cancer Letters, 116(1), 85-92. doi: 10. 1016/S0304-3835(97) 00170-5.
75. Cemazar, M., Todorovic, V., Scancar, J., Lampreht, U., Stimac, M., Kamensek, U., et al. (2015). Adjuvant TNF-alpha therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness. Radiology and Oncology, 49(1), 32-40. doi: 10. 1515/raon-2015-0005.
76. Sedlar, A., Dolinsek, T., Markelc, B., Prosen, L., Kranjc, S., Bosnjak, M., et al. (2012). Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicity. Radiology and Oncology, 46(4), 302-311. doi: 10. 2478/v10019-012-0044-9.
77. Kishida, T., Asada, H., Itokawa, Y., Yasutomi, K., Shin-Ya, M., Gojo, S., et al. (2003). Electrochemo-gene therapy of cancer: intratumoral delivery of interleukin-12 gene and bleomycin synergistically induced therapeutic immunity and suppressed subcutaneous and metastatic melanomas in mice. Molecular Therapy, 8(5), 738-745.
78. Torrero, M. N., Henk, W. G., & Li, S. (2006). Regression of highgrade malignancy in mice by bleomycin and interleukin-12 electrochemogenetherapy. Clinical Cancer Research, 12(1), 257-263. doi: 10. 1158/1078-0432. CCR-05-1514.
79. Reed, S. D., Fulmer, A., Buckholz, J., Zhang, B., Cutrera, J., Shiomitsu, K., et al. (2010). Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs. Cancer Gene Therapy, 17(7), 457-464. doi: 10. 1038/cgt. 2010. 6.
80. Cutrera, J., King, G., Jones, P., Kicenuik, K., Gumpel, E., Xia, X., et al. (2015). Safe and effective treatment of spontaneous neoplasms with interleukin 12 electro-chemo-gene therapy. Journal of Cellular and Molecular Medicine, 19(3), 664-675. doi: 10. 1111/jcmm. 12382.
81. Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Perez Gracia, J. L., & Haanen, J. (2015). Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nature Reviews Cancer, 15(8), 457-472. doi: 10. 1038/nrc3973.
82. Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine, 363(8), 711-723. doi: 10. 1056/Nejmoa1003466.
83. Zitvogel, L., & Kroemer, G. (2012). Targeting PD-1/PD-L1 interactions for cancer immunotherapy. Oncoimmunology, 1(8), 1223-1225. doi: 10. 4161/onci. 21335.
84. Brizio, M., Fava, P., Astrua, C., Cavaliere, G., & Savoia, P. (2015). Complete regression of melanoma skin metastases after electrochemotherapy plus ipilimumab treatment: an unusual clinical presentation. European Journal of Dermatology, 25(3), 271-272. doi: 10. 1684/ejd. 2015. 2522.
85. Mozzillo, N., Simeone, E., Benedetto, L., Curvietto, M., Giannarelli, D., Gentilcore, G., et al. (2015). Assessing a novel immuno-oncology-based combination therapy: ipilimumab plus electrochemotherapy. Oncoimmunology, 4(6), e1008842. doi: 10. 1080/2162402X. 2015. 1008842.