DOI QR코드

DOI QR Code

Adoptive Immunotherapy for Small Cell Lung Cancer by Expanded Activated Autologous Lymphocytes: a Retrospective Clinical Analysis

  • Zhang, Guo-Qing (First Department of Medical Oncology, Chinese PLA General Hospital) ;
  • Li, Fang (First Department of Medical Oncology, Chinese PLA General Hospital) ;
  • Sun, Sheng-Jie (First Department of Medical Oncology, Chinese PLA General Hospital) ;
  • Hu, Yi (First Department of Medical Oncology, Chinese PLA General Hospital) ;
  • Wang, Gang (Laboratory of Tumor Research Center, Chinese PLA General Hospital) ;
  • Wang, Yu (Beijing Immunotech Applied Science Limited) ;
  • Cui, Xiao-Xia (Beijing Immunotech Applied Science Limited) ;
  • Jiao, Shun-Chang (First Department of Medical Oncology, Chinese PLA General Hospital)
  • Published : 2015.03.09

Abstract

Background: To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). Materials and Methods: A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. Results: After culture and proliferation in vitro, the percentages of $CD3^+$, $CD3^+CD8^+$, $CD45RO^+$, $CD28^+$, $CD29^+$, $CD8^+CD28^+$ and $CD3^+CD16^+/CD56^+$ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy${\leq}6$ cycles were obviously prolonged after EAAL immunotherapy. Conclusions: In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients.

Keywords

Adoptive immunotherapy;small cell lung cancer;expanded activated autologous lymphocytes

References

  1. Ahn YO, Kim S, Kim TM, et al (2013). Irradiated and activated autologous PBMCs induce expansion of highly cytotoxic human NK cells in vitro. J Immunother, 36, 373-81. https://doi.org/10.1097/CJI.0b013e3182a3430f
  2. Ahmed Ali HA, Di J, Mei W, et al (2014). Antitumor Activity of Lentivirus-mediated interleukin-12 gene modified dendritic cells in human lung cancer in vitro. Asian Pac J Cancer Prev, 15, 611-6. https://doi.org/10.7314/APJCP.2014.15.2.611
  3. Besser MJ, Shapira-Frommer R, Treves AJ, et al (2010). Clinical responses in a phase II study using adoptive transfer of shortterm cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res, 16, 2646-55. https://doi.org/10.1158/1078-0432.CCR-10-0041
  4. Boissonnas A, Licata F, Poupel L, et al (2013). $CD8^{+}$ tumorinfiltrating T cells are trapped in the tumor-dendritic cell network. Neoplasia, 15, 85-94. https://doi.org/10.1593/neo.121572
  5. Binsfeld M, Fostier K, Muller J, et al (2014). Cellular immunotherapy in multiple myeloma: Lessons from preclinical models. Biochim Biophys Acta, 1846, 392-404.
  6. Costantino CM, Baecher-Allan CM, Hafler DA, et al (2008). Human regulatory T cells and autoimmunity. Eur J Immunol, 38, 921-4. https://doi.org/10.1002/eji.200738104
  7. Cho D, Shook DR, Shimasaki N, et al (2010). Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin Cancer Res, 16, 3901-9. https://doi.org/10.1158/1078-0432.CCR-10-0735
  8. Corthay A (2014). Does the immune system naturally protect against cancer? Front Immunol, 12, 197.
  9. Guo H, Qian X (2010). Clinical applications of adoptive natural killer cell immunotherapy for cancer: current status and future prospects. Onkologie, 33, 389-95.
  10. Hara M, Matsuzaki Y, Shimizu T, et al (2007). Preoperative peripheral naive/memory ratio and prognosis of non smallcell lung cancer patients. Ann Thorac Cardiovasc Surg, 13, 384-90.
  11. Hosoi A, Matsushita H, Shimizu K, et al (2014). Adoptive cytotoxic T lymphocyte therapy triggers a counter-regulatory immunosuppressive mechanism via recruitment of myeloidderived suppressor cells. Int J Cancer, 134, 1810-22. https://doi.org/10.1002/ijc.28506
  12. Jakel CE, Vogt A, Gonzalez-Carmona MA, et al (2014). Clinical studies applying cytokine-induced killer cells for the treatment of gastrointestinal tumors. J Immunol Res, 2014, 897214.
  13. Kato M, Goto S, Soma G (2010). Lymphokine-activated killer cell therapy combined with high-dose glucocorticoid showed clinical efficacy towards advanced lung carcinoma. Anticancer Res, 30, 3125-8.
  14. Kelderman S, Schumacher TN, Haanen JB (2014). Acquired and intrinsic resistance in cancer immunotherapy. Mol Oncol, 8, 1132-9. https://doi.org/10.1016/j.molonc.2014.07.011
  15. Leitner J, Grabmeier-Pfistershammer K, Steinberger P (2010). Receptors and ligands implicated in human T cell costimulatory processes. Immunol Lett, 128, 89-97. https://doi.org/10.1016/j.imlet.2009.11.009
  16. Luo J, Wu FY, Li AW, et al (2012). Comparison of vinorelbine, ifosfamide and cisplatin (NIP) and etoposide and cisplatin (EP) for treatment of advanced combined small cell lung cancer (cSCLC) patients: a retrospective study. Asian Pac J Cancer Prev, 13, 4703-6. https://doi.org/10.7314/APJCP.2012.13.9.4703
  17. Levy B, Saxena A, Schneider BJ (2013). Systemic therapy for small cell lung cancer. J Natl Compr Canc Netw, 11, 780-7. https://doi.org/10.6004/jnccn.2013.0100
  18. Noguchi A, Kaneko T, Naitoh K, et al (2014). Impaired and imbalanced cellular immunological status assessed in advanced cancer patients and restoration of the T cell immune status by adoptive T-cell immunotherapy. Int Immunopharmacol, 18, 90-7. https://doi.org/10.1016/j.intimp.2013.11.009
  19. Pitini V, Arrigo C, Naro C, et al (2007). Interleukin-2 and lymphokine-activated killer cell therapy in patients with relapsed B-cell lymphoma treated with rituximab. Clin Cancer Res, 13, 5497. https://doi.org/10.1158/1078-0432.CCR-07-1115
  20. Phan GQ, Rosenberg SA (2013). Adoptive cell transfer for patients with metastatic melanoma: the potential and promise of cancer immunotherapy. Cancer Control, 20, 289-97. https://doi.org/10.1177/107327481302000406
  21. Qian X, Wang X, Jin H (2014). Cell transfer therapy for cancer: past, present, and future. J Immunol Res, 2014, 525913.
  22. Qian YD, Xu X, Wang L, Huang XE (2014).Clinical safety of chemotherapy for elderly cancer patients complicated with hypertension. Asian Pac J Cancer Prev, 15, 9875-7. https://doi.org/10.7314/APJCP.2014.15.22.9875
  23. Rajbhandary S, Zhao MF, Zhao N, et al (2013). Multiple cytotoxic factors involved in IL-21 enhanced antitumor function of CIK cells signaled through STAT-3 and STAT5b pathways. Asian Pac J Cancer Prev, 14, 5825-31. https://doi.org/10.7314/APJCP.2013.14.10.5825
  24. Sun Z, Shi L, Zhang H, et al (2011). Immune modulation and safety profile of adoptive immunotherapy using expanded autologous activated lymphocytes against advanced cancer. Clin-Immunol, 138, 23-32. https://doi.org/10.1016/j.clim.2010.08.012
  25. Spigel DR, Greco FA, Rubin MS, et al (2012). Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage smallcell lung cancer. Lung Cancer, 77, 359-64. https://doi.org/10.1016/j.lungcan.2012.03.009
  26. Sabado RL, Bhardwaj N (2013). Dendritic cell immunotherapy. Ann N Y Acad Sci, 1284, 31-45. https://doi.org/10.1111/nyas.12125
  27. Saito S, Harada Y, Morodomi Y, et al (2013). Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood. Hum Gene Ther Methods, 24, 241-52. https://doi.org/10.1089/hgtb.2012.183
  28. Shi S, Wang R, Chen Y, et al (2013). Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models. PLoS One, 8, 65757. https://doi.org/10.1371/journal.pone.0065757
  29. Song J, Zhang J, Wang J, et al (2014). ${\beta}1$ integrin modulates tumor growth and apoptosis of human colorectal cancer. Oncol Rep, 32, 302-8. https://doi.org/10.3892/or.2014.3168
  30. Takayama T, Sekine T, Makuuchi M, et al (2000). Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomized trial. Lancet, 356, 802-7. https://doi.org/10.1016/S0140-6736(00)02654-4
  31. Vesely MD, Schreiber RD (2013). Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Ann NY Acad Sci, 1284, 1-5. https://doi.org/10.1111/nyas.12105
  32. Wang WJ, Tao Z, Gu W, et al (2013). Variation of blood T lymphocyte subgroups in patients with non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 4671-3. https://doi.org/10.7314/APJCP.2013.14.8.4671
  33. Wang E, Zhang Q, Liu X, et al (2014). The dual-functional capability of cytokine-induced killer cells and application in tumor immunology. Hum Immunol, 2014, [Epub ahead of print].
  34. Wang X, Yu W, Li H, et al (2014). Can the dual-functional capability of CIK cells be used to improve antitumor effects? Cell-Immunol, 287, 18-22. https://doi.org/10.1016/j.cellimm.2013.11.009
  35. Weber JS (2014). At the bedside: adoptive cell therapy for melanoma-clinical development. J Leukoc Biol, 95, 875-82. https://doi.org/10.1189/jlb.0513293
  36. Xiao Y, Liu J, Huang XE, et al (2014) Clinical study on fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain. Asian Pac J Cancer Prev, 15,10445-9.
  37. Yang L, Ren B, Li H, et al (2013). Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients. Cancer-Immunol-Immunother, 62, 65-73. https://doi.org/10.1007/s00262-012-1311-8
  38. Yu X, He J, Mongkhoune S, et al (2013). Artificial antigenpresenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8+ CD28+ T lymphocyte responses. Asian Pac J Trop Med, 6, 467-72. https://doi.org/10.1016/S1995-7645(13)60076-0
  39. Zhou H, Zeng C, Wei Y, et al (2013). Duration of chemotherapy for small cell lung cancer: a meta-analysis. PLoS One, 8, 73805. https://doi.org/10.1371/journal.pone.0073805
  40. Zhu JM, Yu PW (2013). Effects of Tiam 1 on invasive capacity of gastric cancer cells in vitro and underlying mechanisms. Asian Pac J Cancer Prev, 14, 201-8. https://doi.org/10.7314/APJCP.2013.14.1.201
  41. Zhan P, Liu L, Liu B, et al (2014). Expression of integrin ${\beta}1$ and its significance in squamous cell carcinoma of the cervix. Mol Med Rep, 9, 2473-8. https://doi.org/10.3892/mmr.2014.2134