Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody enhances antitumor efficacy in renal cell carcinoma-bearing mice

Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody enhances antitumor efficacy in renal cell carcinoma-bearing mice

Background/aim: Dendritic cell-based vaccine therapy for renal cell carcinoma is effective but requires improvement. Here we explored whether combination therapy with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor efficacy in renal cell carcinoma-bearing mice. Materials and methods: Balb/c mice were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated or were treated with Renca tumor lysate-pulsed dendritic cells (i.e. dendritic cell-based vaccine), anti-CD69 antibody, or a combination of Renca tumor lysate-pulsed dendritic cells with anti-CD69 antibody. The mice were sacrificed on day 28. Tumor volume was measured for analysis of antitumor efficacy. Spleens were excised to evaluate antitumor immunological responses by measuring the proliferation and activation of T cells, which have the capacity to recognize and destroy tumor cells. Results: Combination treatment with Renca tumor lysate-pulsed dendritic cells and anti-CD69 antibody resulted in significant decreases in tumor volume and significant increases in T-cell proliferation and activity, compared with no treatment or either treatment alone. Conclusion: These findings indicate that anti-CD69 antibody can potentiate antitumor efficacy of dendritic cell-based vaccine. The augmented therapeutic efficacy conferred by the combination therapy may be associated with increased T-cell proliferation and activity.

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  • 1. Jonasch E,  Gao J,  Rathmell WK. Renal cell carcinoma. BMJ 2014; 349: g4797.
  • 2. Wunderlich H, Schumann S, Janitzky V, Moravek P, Podhola M,  Kosmehl H,  Schubert J. Increased incidence of renal cell carcinoma in central Europe. Does diagnostic increase reflect a true increase in incidence? Urologe A 1999; 38: 252-257.
  • 3. Gupta K,  Miller JD,  Li JZ,  Russell MW,  Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 2008; 34: 193-205.
  • 4. Breda A,  Konijeti R,  Lam JS. Patterns of recurrence and surveillance strategies for renal cell carcinoma following surgical resection. Expert Rev Anticancer Ther 2007; 7: 847- 862.
  • 5. Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003; 30: 843-852.
  • 6. Patil S, Manola J, Elson P, Negrier S, Escudier B, Eisen T, Atkins M, Bukowski R, Motzer RJ. Improvement in overall survival of patients with advanced renal cell carcinoma: prognostic factor trend analysis from an international data set of clinical trials. J Urol 2012; 188: 2095-2100.
  • 7. Gleave ME, Elhilali M, Fradet Y, Davis I, Venner P, Saad F, Klotz LH, Moore MJ, Paton V, Bajamonde A. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group. N Engl J Med 1998; 338: 1265-1271.
  • 8. Oliver RT,  Nethersell AB,  Bottomley JM. Unexplained spontaneous regression and alpha-interferon as treatment for metastatic renal carcinoma. Br J Urol 1989; 63: 128-131.
  • 9. Noessner E,  Brech D,  Mendler AN,  Masouris I,  Schlenker R,  Prinz PU. Intratumoral alterations of dendritic-cell differentiation and CD8(+) T-cell anergy are immune escape mechanisms of clear cell renal cell carcinoma. Oncoimmunology 2012; 1: 1451-1453.
  • 10. Heine A, Holderried TA, Brossart P. Immunotherapy in renal cell carcinoma. Immunotherapy 2009; 1: 97-107.
  • 11. Abe H, Kamai T. Recent advances in the treatment of metastatic renal cell carcinoma. Int J Urol 2013; 20: 944-955.
  • 12. Cohen HT,  McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005; 353: 2477-2490.
  • 13. Soerensen AV, Donskov F, Hermann GG, Jensen NV, Petersen A, Spliid H, Sandin R, Fode K, Geertsen PF. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: results from the Danish Renal Cancer Group (DARENCA) study-2. Eur J Cancer 2014; 50: 553-562.
  • 14. Steinman RM,  Banchereau J. Taking dendritic cells into medicine. Nature 2007; 449: 419-426.
  • 15. Perica K,  Varela JC,  Oelke M,  Schneck J. Adoptive T cell immunotherapy for cancer. Rambam Maimonides Med J 2015; 6:e0004.
  • 16. Aruga A, Aruga E, Cameron MJ, Chang AE. Different cytokine profiles released by CD4+ and CD8+ tumor-draining lymph node cells involved in mediating tumor regression. J Leukoc Biol 1997; 61: 507-516.
  • 17. Draube A, Klein-González N, Mattheus S, Brillant C, Hellmich M,  Engert A,  von Bergwelt-Baildon M. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS One 2011; 6: e18801.
  • 18. Miller AB,  Hoogstraten B,  Staquet M,  Winkler A. Reporting results of cancer treatment. Cancer 1981; 47: 207-214.
  • 19. Llera AS,  Viedma F,  Sánchez-Madrid F,  Tormo J. Crystal  structure  of the  C-type  lectin-like  domain  from the human hematopoietic cell receptor CD69. J Biol Chem 2001; 276: 7312-7319.
  • 20. Li J, Andreyev O, Chen M, Marco M, Iwase H, Long C, Ayares D,  Shen Z,  Cooper DK,  Ezzelarab MB. Human T cells upregulate CD69 after coculture with xenogeneic geneticallymodified pig mesenchymal stromal cells. Cell Immunol 2013; 285: 23-30.
  • 21. Ziegler SF, Ramsdell F, Alderson MR. The activation antigen CD69. Stem Cells 1994; 12: 456-465.
  • 22. Alari-Pahissa E, Vega-Ramos J, Zhang JG, Castaño AR, Turley SJ,  Villadangos JA,  Lauzurica P. Differential effect of CD69 targeting on bystander and antigen-specific T cell proliferation. J Leukoc Biol 2012; 92: 145-158.
  • 23. Lim DS, Kim JH, Lee DS, Yoon CH, Bae YS. DC immunotherapy is highly effective for the inhibition of tumor metastasis or recurrence, although it is not efficient for the eradication of established solid tumors. Cancer Immunol Immunother 2007; 56: 1817-1829.
  • 24. Teng L, Chen Y, Ding D, Dai H, Liu G, Li C. Immunosuppressive effect of renal cell carcinoma on phenotype and function of dendritic cells. Int Urol Nephrol 2014; 46: 915-920.
  • 25. Wang J,  Liao L,  Tan J. Dendritic cell-based vaccination for renal cell carcinoma: challenges in clinical trials. Immunotherapy 2012; 4: 1031-1042.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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