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

Abstract

IntroductionRenal cell carcinoma accounts for 4% of all malignant tumors (1) and has an incidence of about 8-9 persons per 100,000 each year, which is increasing (2). There is no obvious symptom in the early stage of this cancer. As a result, approximately 25%-30% of patients exhibit tumor metastasis at first diagnosis and lose the opportunity for surgery (3). Although patients with primarily localized renal cell carcinoma can be successfully treated by partial or radical nephrectomy, one third of cases will subsequently develop metastases (4,5). Therapy of metastatic renal cell carcinoma is particularly difficult because of its poor response to radiotherapy or chemotherapy. Therefore, the prognosis for patients with metastatic renal cell carcinoma is poor, and the survival rate for 5 years is less than 10% (6). These lead to a rising demand for other treatment modalities.Prospective studies note spontaneous regression rates of up to 7% in patients with metastatic renal cell carcinoma (7,8). In addition, immunohistochemical studies of renal cell carcinoma often reveal tumor-infiltrating dendritic cells and T lymphocytes able to recognize and kill tumor cells (9). Therefore, renal cell carcinoma is considered an immunogenic tumor. These findings also lead to attempts to develop immunotherapeutic strategies using immunostimulatory cytokines such as interleukin-2 and interferon-α (10). It has been reported that treatment with interleukin-2 and interferon-α can induce antitumor activity in less than 20% of patients with metastatic renal cell carcinoma, but is associated with a high incidence 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 as...

Increased death and exhaustion of CD69high T cells and NK cells are associated with PD-1 antibody application in the in vitro co-culture system

“…4C , 4E and 4F . Consistent with our results, some researchers found that anti-CD69 antibody can potentiate antitumor efficacy of dendritic cell-based vaccine, which is considered to be associated with increased T-cell proliferation and activity ( Wei et al, 2017 ). Others also found that CD69 deficient mice challenged with prostate carcinoma showed greatly reduced tumor growth and prolonged survival, which be due to the enhanced anti-tumor response of lymphocytes and increased lymphocytes in local ( Esplugues et al, 2003 ).…”

Emerging Strategies of Engineering and Tracking Dendritic Cells for Cancer Immunotherapy

“…75 Tumor lysate and tumor-derived exosomes are also used to activate DCs, and the results show that they can induce T cell activation and proliferation. 76,77 Moreover, it avoids the limitation of antigen selection and is accepted widely by patients. 78,79 All of these approaches have been successful and are simple and cheap.…”

“…The results suggested that DCs pulsed with LY6E peptide antigen strongly matured and activated T cells . Tumor lysate and tumor-derived exosomes are also used to activate DCs, and the results show that they can induce T cell activation and proliferation. , Moreover, it avoids the limitation of antigen selection and is accepted widely by patients. , All of these approaches have been successful and are simple and cheap. We can pulse DCs with antigens that can induce an efficient immune response or combine different antigens from the same tumor to stimulate DCs to improve DC activation.…”

New treatment modalities with vaccine therapy in renal cell carcinoma

“…Wei et al . [31] applied DC-based vaccine and anti-CD69 antibody treatment in murine RCC and reported that anti-CD69 antibody increased antitumor efficiency of DC-based vaccine and caused significant decrease in tumor volume and significant increase in T-cell proliferation and activity.…”