{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:01:50Z","timestamp":1784145710765,"version":"3.55.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and renal cell carcinoma could potentially have long-term disease control with a tag-7 gene-modified tumor cells-based vaccine. Randomized clinical trials in patients whose tumors produce low amounts of immunosuppressive factors are needed to confirm this hypothesis in both the adjuvant and metastatic settings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Immunotherapy may produce long-lasting effects on survival and toxicity. The magnitude of efficacy may be dependent on immune factors. We analyzed the results of a phase I\/II study of a tag-7 gene-modified tumor cells-based vaccine (GMV) in patients with malignant melanoma (MM) or renal cell carcinoma (RCC) with biomarker analysis of immunosuppressive factors (ISFs) production by their tumor cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>From 2001 to 2014, 80 patients received GMV: 68 with MM and 12 with RCC. Treatment in the metastatic setting included 61 patients (MM, 51; RCC, 10), and treatment in the adjuvant setting (after complete cytoreduction) included 19 patients (MM, 17; RCC, 2). Twenty-six patients were stage III (33%), and 54 (67%) were stage IV. The patients\u2019 tumor samples were transferred to culture, transfected with tag-7 gene, and inactivated by radiation. The produced product was injected subcutaneously every 3\u2009weeks until progression or 2\u2009years of therapy. ISFs were measured in the supernatants of the tumor cell cultures and used as predictive factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>No major safety issues or grade 5 adverse events (AEs) were seen. One grade 4 and two grade 3 AEs were registered. No AEs were registered in 89.4% of treatment cycles. No delayed AE was found. The 5-year overall survival (OS) in the intention-to-treat population was 25.1%. There were no differences between MM OS and RCC OS (log rank, p = .44). Median OS in the metastatic setting was 0.7\u2009years and in the adjuvant setting was 3.1\u2009years. Classification trees were built on the basis of ISF production (Fig. 1). The median OS was 6.6\u2009years in the favorable prognosis (FP) group (major histocompatibility complex class I polypeptide-related sequence A [MICA] level \u2264582 pg\/mL, n =\u200915) and 4.6 months in the unfavorable (UF) group (MICA level &amp;gt;582 pg\/mL, n =\u200912; p &amp;lt; .0001). No significant differences were found between classification trees based on ISFs (transforming growth factor \u03b21 [TGF-\u03b21], interleukin-10 [IL-10], and vascular endothelial growth factor [VEGF]). In patients with stage III\u2013IV MM with FP, median OS was 2.3\u2009years, with 31% patients alive at 10\u2009years (Fig.\u20092) in the UF group (0.4\u2009years; log rank, p =\u20091.94E\u22125). No FP patients received modern immunotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>GMV showed high results in carefully selected patients with low ISF (TGF-\u03b21, IL-10, and VEGF) production. The method should be further investigated in patients with FP.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2020-0160","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T18:16:15Z","timestamp":1585851375000},"page":"e1303-e1317","source":"Crossref","is-referenced-by-count":3,"title":["An Open-Label Study of the Safety and Efficacy of <i>Tag-7<\/i> Gene-Modified Tumor Cells-Based Vaccine in Patients with Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer"],"prefix":"10.1093","volume":"25","author":[{"given":"Aleksei Viktorovich","family":"Novik","sequence":"first","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"},{"name":"Department of Oncology, Child Oncology and Ray Therapy, St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Borisovna","family":"Danilova","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maksim Ivanovich","family":"Sluzhev","sequence":"additional","affiliation":[{"name":"Department of Oncology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Leonidovna","family":"Nehaeva","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei Sergeevich","family":"Larin","sequence":"additional","affiliation":[{"name":"Laboratory of Gene Therapy, Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Viktorovich","family":"Girdyuk","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana Anatolevna","family":"Protsenko","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Innovative Technologies, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Igorevna","family":"Semenova","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"},{"name":"Department of Chemotherapy and Innovative Technologies, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksei Olegovich","family":"Danilov","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Diagnostic, Clinical and Research Center of Specialized Types of Medical Care (Oncological), St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir Mikhailovich","family":"Moiseyenko","sequence":"additional","affiliation":[{"name":"Clinical and Research Center of Specialized Types of Medical Care (Oncological), St. Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgii Pavlovich","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Aleksandrovna","family":"Baldueva","sequence":"additional","affiliation":[{"name":"Department of Oncoimmunology, N.N. 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