Abstract
Results of clinical and immunological assessment of autologous dendritic cells (DC) primed with cancer-testis antigens (CTA+DC) are presented in this paper. Nine patients were treated from 2012 to 2014. CTA+dC were obtained from adhesive CD14+ monocytes fraction from peripheral blood of patients. Tumor cell lysate of autologous and/or allogeneic tumor cells expressing immunogenic CTA were used for immature CD1a+ DC load. Mature CD83+ DC were injected intradermal 3 days after IM injection of 300 mg of cyclophosphamide for T-regulatory cells depletion. Interleukin-1beta (Betaleukin) was used as immunologic adjuvant (40000 ME). Nine patients received from 1 to 24 injections of CTA+DC (average - 7) and were evaluable for toxicity and efficacy (bot clinical and immunologic). No objective responses were seen. Stable disease was obtained in 5 (56%) patients. In 4 patients (44%) disease was stable >6 month, in 2 (22%) patients - >12 month. One patient was stable for 17 month. Neither serious adverse events nor grade 3 or 4 adverse events (AE) were registered. Grade 1 or 2 AE were seen in 6/9 patients. No therapy for this AE was needed. DHT reactions was registered in 7/9 patients (78%). Tendency for increasing number of activated T-cells and decreasing of regulatory T-cells was seen in peripheral blood during patients’ vaccination.References
Акинфиева О.В., Бубнова Л.М., Бессмельцев С.С. NKT-клетки: характерные свойства и функциональная значимость для регуляции иммунного ответа // Онкогематология. - 2010. - № 4. - Р. 39-48
Барышников А.Ю., Демидов Л.В., Михайлова И.Н., Петенко Н.Н. Вакцинотерапия рака: от эксперимента к клинике // Вестн. Росс. Акад. Мед. наук. - 2007. - № 10. - C. 46-48.
Михайлова И.Н., Иванов П.В., Петенко Н.Н. Внутрикожная клеточная реакция на фоне вакцинотерапии меланомы кожи // Росс. биотерап. журнал. - 2010. - № 1. - С. 63-67.
Нехаева Т.Л. Оптимизация аутологичных дендритноклеточных вакцин для лечения больных злокачественными новообразованиями // Сиб. онкол. журнал. - 2013. - № 3 (57). - С. 52-56.
Caballero O.L., Chen Y.T. Cancer/testis (CT) antigens: potential targets for immunotherapy // Cancer Sci. - 2009. - Vol. 100 (11). - P. 2014-2021.
Dagher R., Long L.M., Read E.J. et al. Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study // Med. Pediatric Oncol. - 2002. - Vol. 38 (3). - P. 158-164.
Dillman R., Barth N., Selvan S., et al. Phase I/II trial of autologous tumor cell line-derived vaccines for recurrent or metastatic sarcomas // Cancer Biother. Radiopharm. - 2004. - Vol. 19 (5). - P. 581-588.
Emori M., Tsukahara T., Kawaguchi S., Wada T. Peptide vaccination therapy for bone and soft tissue sarcoma // Nihon Rinsho. - 2011. - Vol. 69 (9). - P. 1670-1673.
Ferry J.A., Sohani A.R., Longtine J.A. et al. HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma // Mod. Pathol. - 2009. - Vol. 22 (5). - P. 618-626.
Geiger J.D., Hutchinson R.J., Hohenkirk L.F. et al. Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T. cells and mediate tumor regression // Cancer Research. - 2001. - Vol. 61 (23). - P. 8513-8519.
Ida K., Kawaguchi S., Sato Y. et al. Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A2402 anchor substitute // J.Immunol. - 2004. - Vol. 173(2). - P. 1436-1443.
Imyanitov E.N., Suspitsin E.N., Buslov K.G. et al. Isolation of nucleic acids from paraffin-embedded archival tissues and other difficult sources / in Kieleczawa J. (ed): The DNA Book: Protocols and Procedures for the Modern Molecular Biology Laboratory // Sudbury, M.A., Jones and Bartlett Publishers, 2006. - P. 85-97.
Kawaguchi S., Wada T., Ida K. et al. Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma // J. Translational Med. - 2005. - Vol. 3. - P. 1.
Maki R.G. Soft tissue sarcoma as a model disease to examine cancer immunotherapy // Curr. Opin. Oncol. - 2001. - Vol. 13 (4). - P. 270-274.
Maki R.G. Future directions for immunotherapeutic intervention against sarcomas // Curr. Opin. Oncol. - 2006. - Vol. 18 (4). - P. 363-368.
Pollack S.M., Loggers E.T., Rodler E.T. et al. Immune-based therapies for sarcoma // Sarcoma. - 2011. - Vol. 2011. - P. 438940.
Robbins P.F., Morgan R.A., Feldman S.A. et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1 // J. Clin. Oncol. - 2011. - Vol. 1; 29 (7). - P. 917-924.
Skubitz K.M., Pambuccian S., Carlos J.C., Skubitz A.PN. Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors // J. Translational Medicine. - 2008. - Vol. 6. - P. 23.
Suminoe A., Matsuzaki A., Hattori H. et al. Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors // Pediatric Transplantation. - 2009. - Vol. 13 (6). - P. 746-753.
Xie S., Wu X., Zhang G. et al. Remarkable regression of a lung recurrence from an undifferentiated embryonal sarcoma of the liver treated with a DC vaccine combined with immune cells: A. case report // Cell Immunol. - 2014. - Vol. 290 (2). - P. 185-189.
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