Enhance the anti-renca carcinoma effect of a DNA vaccine targeting G250 gene by co-expression with cytotoxic T-lymphocyte associated antigen-4(CTLA-4)

Zhao, Youguang; Wei, Zhitao; Yang, Hang; Li, Xiaowei; Wang, Qiwu; Wang, Liang; Li, Shadan

doi:10.1016/j.biopha.2017.03.015

Cited by 13 publications

(9 citation statements)

References 16 publications

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“… 23 , 24 Studies have reported that various vaccines based on CAIX antigen can effectively stimulate antigen-specific immune responses and inhibit the growth of renal cancer. 25 , 26 The preliminary results of our research group also confirm that CAIX vaccine with the help of the adjuvant can induce antigen-specific multi-functional CD8 T cell immune response and suppress the tumor growth of renal cancer. 27 These results indicate that the developed DNA vaccine based on CAIX antigen is an effective way to treat renal cancer.…”

Section: Introductionsupporting

confidence: 59%

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Chai

Qin

Shi

et al. 2022

Molecular Therapy - Oncolytics

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Tumor DNA vaccine as an effective therapeutic approach can induce systemic immunity against malignant tumors, but its therapeutic effect is still not satisfactory in advanced renal cancer. Herein, a novel DNA vaccine containing dual antigens of fibrinogen-like protein 1 (FGL1) and carbonic anhydrase IX (CAIX) was developed and intramuscularly delivered by PLGA/PEI nanoparticles for renal cancer therapy. Compared with PLGA/PEI-pCAIX immunization, PLGA/PEI-pFGL1/pCAIX co-immunization significantly inhibited the subcutaneous tumor growth and promoted the differentiation and maturation of CD11c + DCs and CD11c + CD11b + DCs subset. Likewise, the increased capabilities of CD8 T cell proliferation, CTL responses, and multi-functional CD8 + T cell immune responses were observed in PLGA/PEI-pFGL1/pCAIX vaccine group. Interestingly, depletion of CD8 + T cells by using CD8 mAb resulted in a loss of anti-tumor function of PLGA/PEI-pFGL1/pCAIX vaccine, suggesting that the anti-tumor activity of the vaccine was dependent on CD8 + T cell immune responses. Furthermore, PLGA/PEI-pFGL1/pCAIX co-immunization also suppressed the lung metastasis of tumor mice by enhancing the multi-functional CD8 + T cell responses. Therefore, these results indicate that PLGA/PEI-pFGL1/pCAIX vaccine could provide an effective protective effect for renal cancer by enhanced DC-mediated multi-functional CD8 + T cell immune responses. This vaccine strategy offers a potential approach for solid or metastatic tumor treatment.

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Section: Introductionsupporting

confidence: 59%

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Chai

Qin

Shi

et al. 2022

Molecular Therapy - Oncolytics

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“…Several clinical trials of anti‐PD‐1/PD‐L1 antibodies (NCT03308396, NCT02771626, NCT03066427) are undergoing for the treatment of RCC. Previous studies have also demonstrated the effectiveness of anti‐CTLA‐4 antibodies in eliminating RCC cells, as well as a correlation between RCC and the expression levels of CTLA‐4 and PD‐1/PD‐L1 . Tumor microenvironment factors such as tumor‐infiltrating lymphocytes (TIL) can affect the sensitivity to anti‐CTLA‐4 and anti‐PD‐1/PD‐L1 therapy .…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have also demonstrated the effectiveness of anti-CTLA-4 antibodies in eliminating RCC cells, 13 as well as a correlation between RCC and the expression levels of CTLA-4 and PD-1/PD-L1. [14][15][16] Tumor microenvironment factors such as tumor-infiltrating lymphocytes (TIL) can affect the sensitivity to anti-CTLA-4 and anti-PD-1/PD-L1 therapy. 17,18 Therefore, for a better understanding of immunotherapy in RCC, it is important to explore the level of TIL and the expression levels of CTLA-4 and PD-L1.…”

mentioning

confidence: 99%

An immunophenotyping of renal clear cell carcinoma with characteristics and a potential therapeutic target for patients insensitive to immune checkpoint blockade

Zhao

Yang

et al. 2019

J of Cellular Biochemistry

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Renal clear cell carcinoma (RCC) patients who do not achieve optimal control of progression with immune checkpoint blockade (ICB) should be further studied. Unsupervised consensus clustering was used to group 525 RCC patients based on two typical ICB pathways, CTLA-4 and pogrammed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1), as well as two new discovered regulators, CMTM6 and CMTM4. Three immune molecular subtypes (IMMSs) with different clinical and immunological characteristics were identified (type I, II, and III), among which there were more stage I and low-grade tumors in type I RCC than in type II and III. The proportion of males was highest in type II RCC. Overall survival of type II and III was similar (5.2 and 6 years) and statistically shorter than that of type I (7.6 years) before and after adjusting for age and gender. When conducting stratified analysis, our IMMSs were able to identify high-risk patients among middle-aged patients, males, and stage IV patients.Among the differentially expressed genes, approximately 84% were highly expressed in type II and III RCC. Genes related to ICB (CTLA-4, CD274, and PDCD1LG2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type II and III RCC. These results documented that patients with type II and III cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. High expression of CMTM4 in type I RCC (69%) and a statistically significant interaction of CD274 and CMTM6 indicated that CMTM4/6 might be new therapy targets for type I, who are resistant to ICB.

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“…13 Recent years, various vaccines based CAIX antigen have been manufactured for tumor immunotherapy. 14,15 We and others had demonstrated CAIX-based DNA vaccine could induce antigenspecific CD8 + T cell immune response with the help of adjuvant, and inhibit the tumor growth of renal carcinoma. [16][17][18] But the challenges of its effectiveness and safety remain huge in clinical application in the future.…”

Section: Introductionmentioning

confidence: 99%

Co‐immunization with L‐Myc enhances CD8⁺ or CD103⁺ DCs mediated tumor‐specific multi‐functional CD8⁺ T cell responses

Chai¹,

Zhang

Jiang

et al. 2021

Cancer Science

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Enhance the anti-renca carcinoma effect of a DNA vaccine targeting G250 gene by co-expression with cytotoxic T-lymphocyte associated antigen-4(CTLA-4)

Cited by 13 publications

References 16 publications

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

An immunophenotyping of renal clear cell carcinoma with characteristics and a potential therapeutic target for patients insensitive to immune checkpoint blockade

Co‐immunization with L‐Myc enhances CD8⁺ or CD103⁺ DCs mediated tumor‐specific multi‐functional CD8⁺ T cell responses

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Enhance the anti-renca carcinoma effect of a DNA vaccine targeting G250 gene by co-expression with cytotoxic T-lymphocyte associated antigen-4(CTLA-4)

Cited by 13 publications

References 16 publications

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

An immunophenotyping of renal clear cell carcinoma with characteristics and a potential therapeutic target for patients insensitive to immune checkpoint blockade

Co‐immunization with L‐Myc enhances CD8+ or CD103+ DCs mediated tumor‐specific multi‐functional CD8+ T cell responses

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Co‐immunization with L‐Myc enhances CD8⁺ or CD103⁺ DCs mediated tumor‐specific multi‐functional CD8⁺ T cell responses