Use of lectins to promote oligomerization of glycoproteins and antigenic molecules
A lectin and antigen technology, applied in the direction of cancer antigen components, peptide/protein components, vertebrate antigen components, etc., can solve problems such as differences in legume lectins
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Embodiment 1
[0376] 6. Example 1: Consistently Elevated Levels of CON A in Human GP96-Peptide Complex Batches
[0377] Tissue homogenates (A to D) from 4 independent human kidney tumor samples were prepared and processed by Con A column chromatography. The Con A eluate was separated and half of the material was set aside. The remaining samples were buffer exchanged to PBS (PD-10 column) followed by further purification of 2 samples over split DEAE columns to generate 2 homogenate-matched final products - 1 with no buffer between Con A and DEAE columns One with a buffer exchange step (Bx) between the two columns. Con A concentrations in these isolated gp96-peptide samples were then determined using a sensitive ELISA for the detection of Con A.
[0378] Concanavalin A specific ELISA:
[0379] Materials: Concanavalin A was purchased from Sigma, catalog number C7275. Capture Antibody: Mouse Anti-Con A Cat. No. MAB 158 Maine Biotechnology, Primary Antibody: Rabbit Anti-Con A Cat. No. C740...
Embodiment 2
[0382] 7. Example 2: CON A exists in an oligomerized molecular complex
[0383] Common homogenates from chemically induced murine fibrosarcoma (Meth A) tissue were prepared and processed by Con A column chromatography. The Con A eluate was separated and half of the material was set aside. The remaining samples were buffer exchanged to PBS, followed by further purification of 2 samples over split DEAE columns to generate 2 homogenate-matched final products - 1 with no buffer exchange between Con A and DEAE columns (no Bx) , 1 with buffer exchange step (Bx). The 2 samples and samples of free Con A (5 μg, 50 μg / mL) were fractionated together by SEC on a Superdex200 column (upper, middle and lower, respectively). Collected fractions were analyzed by SDS-PAGE for gp96 (fractions 1 to 8; inset), and individual fractions were evaluated for Con A content by direct ELISA against Con A (fractions 1 to 14; overlay) (for Con A For direct ELISA of A, see Example 1). There was only a sm...
Embodiment 3
[0385] 8. Example 3: Oligomerization Response Correlates with In Vitro and In Vivo Potency
[0386] 8.1. Con A content in human gp96 samples correlates with potency in vitro
[0387] gp96 samples were prepared from 4 independent human kidney tumor samples (A to D) as described above (see figure 1 ), generating 4 pairs of samples that differed only in the inclusion or omission of the buffer exchange step between the Con A and DEAE columns. Using the CD71 system, the con A content of all eight samples was determined (panel A; see also figure 1 ) and in vitro antigen re-presentation (Panel B). In each case, material prepared by a method that included a buffer exchange step (and contained high levels of Con A) compared to samples generated from matched tumor homogenates and prepared by a step that omitted the buffer exchange step Has higher in vitro re-presentation activity.
[0388] CD71 in vitro re-presentation assay:
PUM
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