This study describes a novel cancer immunotherapy treatment that exploits the natural anti-Gal Ab to destroy tumor lesions and convert them into an endogenous vaccine targeted to APC via FcγR. Anti-Gal constitutes 1% of immunoglobulins in humans and interacts specifically with α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). The binding of anti-Gal to α-gal epitopes on pig cells mediates xenograft rejection. The proposed method uses glycolipid micelles with multiple α-gal epitopes (α-gal glycolipids). These glycolipids are extracted from rabbit red cell membranes and are comprised of ceramides with carbohydrate chains containing 5-25 carbohydrates, all capped with α-gal epitopes. Efficacy of this treatment was demonstrated in α1,3-galactosyltransferase knockout mice producing anti-Gal and bearing B16 melanoma or B16/OVA producing OVA as a surrogate tumor Ag. These mice are unique among nonprimate mammals in that, similar to humans, they lack α-gal epitopes and can produce the anti-Gal Ab. Intratumoral injection of α-gal glycolipids results in local inflammation mediated by anti-Gal binding to the multiple α-gal epitopes and activation of complement. These glycolipids spontaneously insert into tumor cell membranes. The binding of anti-Gal to α-gal expressing tumor cells induces the destruction of treated lesions as in anti-Gal-mediated xenograft rejection. Anti-Gal further opsonizes tumor cells within the lesion and, thus, targets them for effective uptake by APC that transport the tumor Ags to draining lymph nodes. APC further cross-present immunogenic tumor Ag peptides and elicit a systemic anti-tumor immune response. Similar intratumoral injection of α-gal glycolipids in humans is likely to induce the destruction of treated lesions and elicit a protective immune response against micrometastases.
|Number of pages||12|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Apr 2007|
ASJC Scopus subject areas
- Immunology and Allergy