RGD Reference Report - A DNA vaccine against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) prevents tumor growth. - Rat Genome Database

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A DNA vaccine against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) prevents tumor growth.

Authors: Lan, KH  Liu, YC  Shih, YS  Tsaid, CL  Yen, SH  Lan, KL 
Citation: Lan KH, etal., Biochem Biophys Res Commun. 2013 Oct 18;440(2):222-8. doi: 10.1016/j.bbrc.2013.09.031. Epub 2013 Sep 13.
RGD ID: 7411680
Pubmed: PMID:24041689   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2013.09.031   (Journal Full-text)

Co-stimulatory signaling pathway triggered by the binding of B7.1/B7.2 (CD80/86) of antigen-presenting cells (APCs) to CD28 of T cells is required for optimal T-cell activation. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Ipilimumab, a monoclonal antibody against CTLA-4, has shown positive efficacy in a pivotal clinical trial for the treatment of metastatic melanoma and was approved by FDA. However, the cost of monoclonal antibody-based therapeutics might limit the number of patients treated. To develop a novel therapeutics specifically targeting CTLA-4, we constructed a DNA vaccine by cloning the sequence of CTLA-4 fused with a transmembrane domain sequence of placental alkaline phosphatase (PLAP) into a mammalian expression plasmid, pVAC-1. Immunization with the resulting construct, pVAC-1-hCTLA-4, elicited antibody specific to human CTLA-4 with cross reactivity to murine CTLA-4, which was sufficient for inhibiting B16F10 tumor growth in c57BL/6 mice in the absence of measurable toxicity. Coupling liposome with pVAC-1-mCTLA-4 could break tolerance to self-antigen in BALB/c mice and induce potent immunity against murine CTLA-4, and suppress growth of subcutaneous renal cell carcinoma (Renca).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Melanoma treatmentIMP 7411680 RGD 
Experimental Melanoma treatmentISOCTLA4 (Homo sapiens)7411680; 7411680 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Mus musculus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Homo sapiens)
CTLA4  (cytotoxic T-lymphocyte associated protein 4)


Additional Information