Glycans in immune recognition and response

Area of Science:

• Immunology
• Glycobiology
• Oncology

Background:

• Cell surface glycans are crucial for immune recognition, with cancer cells often exhibiting altered glycosylation patterns.
• Tumor-associated carbohydrate antigens (TACAs) are typically poorly immunogenic, limiting their use in cancer vaccines and antibody therapies.
• Some foreign carbohydrates, like N-glycolylneuraminic acid (Neu5Gc) and alpha-galactosyl (αGal), are immunogenic in humans.

Purpose of the Study:

• To review the immunogenicity of Neu5Gc and its role in human diseases, particularly cancer.
• To compare and contrast Neu5Gc with another foreign immunogenic carbohydrate, αGal.
• To explore the potential of these immunogenic carbohydrates in novel targeted cancer theranostics.

Main Methods:

• Review of existing literature on Neu5Gc and αGal immunogenicity.
• Analysis of the role of Neu5Gc accumulation in carcinoma and subsequent immune responses.
• Evaluation of anti-Neu5Gc and anti-αGal antibody responses in humans.

Main Results:

• Neu5Gc, a dietary sugar, is expressed on carcinoma cells, eliciting a human immune response generating anti-Neu5Gc antibodies.
• The presence of Neu5Gc and anti-Neu5Gc antibodies can contribute to chronic inflammation and disease, including cancer.
• Humans naturally possess circulating anti-αGal antibodies, another foreign immunogenic carbohydrate antigen.

Conclusions:

• Neu5Gc and αGal represent promising targets for novel glycotherapies and theranostics due to their immunogenicity.
• Understanding the interplay between foreign glycans and the human immune system is key to developing effective cancer treatments.
• Targeted therapies utilizing anti-Neu5Gc or anti-αGal antibodies hold potential for cancer treatment and diagnosis.