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Autoantibodies targeting tumor-associated antigens in metastatic cancer: Sialylated IgGs as candidate anti-inflammatory antibodies.

Oaks M, Taylor S, Shaffer J - Oncoimmunology (2013)

Bottom Line: The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid.We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN).The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

View Article: PubMed Central - PubMed

Affiliation: Aurora St. Luke's Medical Center and the Aurora Research Institute; Milwaukee, WI USA.

ABSTRACT
In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations of IgGs may exert anti-inflammatory effects. Here, we describe a population of antibodies that form in the natural course of metastatic cancer and contain glycans that terminate with sialic acid. We demonstrate that both the titer of these antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid. We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN). We propose that these antibodies are candidate anti-inflammatory antibodies. The presence of anti-inflammatory antibodies in cancer patients may explain, at least in part, why tumors persist and spread in the host despite strong tumor-specific humoral responses. The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

No MeSH data available.


Related in: MedlinePlus

Figure 6. Binding of affinity purified anti-NY-ESO-1 antibodies to soluble DC-SIGN. Selected samples (based on material availability) were applied to wells coated with soluble DC-SIGN (sDC-SIGN). Bound IgGs were estimated by comparing the titration of samples on fixed amounts of DC-SIGN, and interpolated from a standard curve generated from IgGs that were directly bound to microwells. Lavender boxes = intact affinity purified IgGs; purple boxes = Sambucus nigra agglutinin (SNA)-lectin depleted IgG (SNA−); yellow boxes = SNA-enriched fraction of IgG (SNA+). Error bars represent standard deviations as obtained from hextuplicate determinations. Representative data from one out of two independent assays are reported.
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Figure 6: Figure 6. Binding of affinity purified anti-NY-ESO-1 antibodies to soluble DC-SIGN. Selected samples (based on material availability) were applied to wells coated with soluble DC-SIGN (sDC-SIGN). Bound IgGs were estimated by comparing the titration of samples on fixed amounts of DC-SIGN, and interpolated from a standard curve generated from IgGs that were directly bound to microwells. Lavender boxes = intact affinity purified IgGs; purple boxes = Sambucus nigra agglutinin (SNA)-lectin depleted IgG (SNA−); yellow boxes = SNA-enriched fraction of IgG (SNA+). Error bars represent standard deviations as obtained from hextuplicate determinations. Representative data from one out of two independent assays are reported.

Mentions: Having established that the binding of IgGs to DC-SIGN is independent of Fab (and its sialylation state), we evaluated the binding of intact, affinity purified anti-NY-ESO-1 antibodies to DC-SIGN (Fig. 6). We observed a clear relationship between the percentage of sialylated antibodies as measured by ELISA and the extent of binding to soluble DC-SIGN. In order to determine whether the binding activity of affinity purified anti-NY-ESO-1 antibodies to DC-SIGN is limited to their sialylated fraction, we evaluated SNA+ and SNA− antibody fractions in binding assays. These analyses demonstrate that the SNA+ antibody fraction is enriched for species that binds soluble DC-SIGN, whereas the SNA− fraction exhibited a markedly DC-SIGN-binding ability. This was true for each patient analyzed. Indeed, the SNA+ IgG fraction of all samples showed the highest DC-SIGN binding potential, the SNA- fraction has a markedly reduced binding activity, and non-fractionated samples bound DC-SIGN to intermediate levels. These data suggest that the DC-SIGN-binding fraction of anti-NY-ESO-1 IgGs from melanoma patients is largely limited to the population of antibodies whose Fc terminates with α2,6-Sia.


Autoantibodies targeting tumor-associated antigens in metastatic cancer: Sialylated IgGs as candidate anti-inflammatory antibodies.

Oaks M, Taylor S, Shaffer J - Oncoimmunology (2013)

Figure 6. Binding of affinity purified anti-NY-ESO-1 antibodies to soluble DC-SIGN. Selected samples (based on material availability) were applied to wells coated with soluble DC-SIGN (sDC-SIGN). Bound IgGs were estimated by comparing the titration of samples on fixed amounts of DC-SIGN, and interpolated from a standard curve generated from IgGs that were directly bound to microwells. Lavender boxes = intact affinity purified IgGs; purple boxes = Sambucus nigra agglutinin (SNA)-lectin depleted IgG (SNA−); yellow boxes = SNA-enriched fraction of IgG (SNA+). Error bars represent standard deviations as obtained from hextuplicate determinations. Representative data from one out of two independent assays are reported.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: Figure 6. Binding of affinity purified anti-NY-ESO-1 antibodies to soluble DC-SIGN. Selected samples (based on material availability) were applied to wells coated with soluble DC-SIGN (sDC-SIGN). Bound IgGs were estimated by comparing the titration of samples on fixed amounts of DC-SIGN, and interpolated from a standard curve generated from IgGs that were directly bound to microwells. Lavender boxes = intact affinity purified IgGs; purple boxes = Sambucus nigra agglutinin (SNA)-lectin depleted IgG (SNA−); yellow boxes = SNA-enriched fraction of IgG (SNA+). Error bars represent standard deviations as obtained from hextuplicate determinations. Representative data from one out of two independent assays are reported.
Mentions: Having established that the binding of IgGs to DC-SIGN is independent of Fab (and its sialylation state), we evaluated the binding of intact, affinity purified anti-NY-ESO-1 antibodies to DC-SIGN (Fig. 6). We observed a clear relationship between the percentage of sialylated antibodies as measured by ELISA and the extent of binding to soluble DC-SIGN. In order to determine whether the binding activity of affinity purified anti-NY-ESO-1 antibodies to DC-SIGN is limited to their sialylated fraction, we evaluated SNA+ and SNA− antibody fractions in binding assays. These analyses demonstrate that the SNA+ antibody fraction is enriched for species that binds soluble DC-SIGN, whereas the SNA− fraction exhibited a markedly DC-SIGN-binding ability. This was true for each patient analyzed. Indeed, the SNA+ IgG fraction of all samples showed the highest DC-SIGN binding potential, the SNA- fraction has a markedly reduced binding activity, and non-fractionated samples bound DC-SIGN to intermediate levels. These data suggest that the DC-SIGN-binding fraction of anti-NY-ESO-1 IgGs from melanoma patients is largely limited to the population of antibodies whose Fc terminates with α2,6-Sia.

Bottom Line: The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid.We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN).The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

View Article: PubMed Central - PubMed

Affiliation: Aurora St. Luke's Medical Center and the Aurora Research Institute; Milwaukee, WI USA.

ABSTRACT
In addition to the well-established effector functions of IgGs, including direct cytotoxicity and antibody-dependent cellular cytotoxicity, some populations of IgGs may exert anti-inflammatory effects. Here, we describe a population of antibodies that form in the natural course of metastatic cancer and contain glycans that terminate with sialic acid. We demonstrate that both the titer of these antibodies and their level of sialylation are relatively stable throughout the progression of metastatic melanoma. The sialylation pattern of these antibodies somehow correlates with their specificity for tumor-associated antigens, as IgGs targeting several antigens associated with infectious agents are relatively poor of sialic acid. We also show that some antibodies targeting the melanoma-associated antigen NY-ESO-1 bind to the human C-type lectin CD209 (DC-SIGN). We propose that these antibodies are candidate anti-inflammatory antibodies. The presence of anti-inflammatory antibodies in cancer patients may explain, at least in part, why tumors persist and spread in the host despite strong tumor-specific humoral responses. The elucidation of the cellular and molecular pathways involved in the induction of anti-inflammatory antibodies specific for tumor-associated antigens and their function may yield important insights into how tumors evade immune detection and progress.

No MeSH data available.


Related in: MedlinePlus